Novel metal complex, method for producing same, and method for producing gamma-lactam compound using same

ABSTRACT

The present invention relates to a novel metal complex, a method for producing same, and a method for producing a gamma-lactam compound using same, and the metal complex according to the present invention is used as a catalyst for producing a gamma-lactam compound and can efficiently produce a gamma-lactam compound with an excellent yield and excellent selectivity.

CROSS-REFERENCE TO RELATED APPLICATION

The present application is a division of U.S. patent application Ser.No. 16/959,880 filed on Jul. 20, 2020 which is a national stage filingunder 35 U.S.C. § 371 of PCT application number PCT/KR2019/000040 filedon Jan. 2, 2019 which is based upon and claims the benefit of prioritiesto Korean Patent Application No. 10-2018-0000449, filed on Jan. 2, 2018and Korean Patent Application No. 10-2018-0172885, filed on Dec. 28,2018, in the Korean Intellectual Property Office, which are incorporatedherein in their entireties by reference.

TECHNICAL FIELD

The present invention relates to a novel metal complex, a method ofpreparing the same, and a method of preparing a gamma-lactam compoundusing the same, and more particularly, to a novel metal complex allowinga gamma-lactam compound to be prepared from a dioxazol-one compound withexcellent selectivity and yield, a method of preparing the same, and amethod of preparing a gamma-lactam compound using the same.

BACKGROUND ART

The most preferred method of purifying hydrocarbon with low added valuewhich is supplied in large quantities in petroleum or a renewablebiomass source into a chemical material with high added value is areaction of oxidizing a C—H bond using a catalyst.

Therefore, the reaction of oxidizing a C—H bond using a catalyst isregarded as being one of the most important reactions in chemistry, anda nitration reaction of an aliphatic compound having a C—H compoundusing a catalyst is a very important reaction which is most commonlyused in various organic synthesis, medicines, and material chemistry.

An effective and general method for performing a C—N coupling reactionis to convert a nucleophilic amino functional group into anelectrophilic nitrene having a much stronger reactivity in a C—Hamidation reaction using a metal catalyst.

This reaction is very efficient and the related reactions have beenstudied by many researchers for a long time.

As an example, it is known by Breslow et al. that in the synthesis ofoxathiazolidine catalyzed by Fe(III) or Rh(II), ROSO₂N═IR′(iminoiodinanes) which is a reactive peroxide may serve as asulfonylnitrene precursor, and thereafter, various methods relatedthereto have been studied.

However, C—H amidation has an unsolved problem for being applied topreparation of cyclic amides such as lactam which is very useful for araw material and an intermediate in organic synthesis and a medicinaluse, and the route thereof is also unclear.

The simplest precursor and the most important intermediate which maydirectly produce a cyclic amide compound is known as carbonylnitreneproduced in an in-situ reaction.

Therefore, in principle, it is considered that in a catalytic reactionusing a metal, the reaction proceeds through a main metal-nitreneintermediate and then a C—H bond is inserted to produce anaziheterocyclic compound corresponding thereto.

However, the main reason for not synthesizing a lactam compound by theC—H amidation reaction is that a metal-carbonylnitrene intermediatewhich is regarded as an intermediate is unstable and easily produceisocyanate by Curtius type rearrangement.

This instability is also accounted for as acyl azide as a synthesisprecursor under photolysis, pyrolysis, and transition metal catalystconditions.

Accordingly, acyl azide is inappropriate as an amide source of a C—Hamidation reaction and a specific amide source is needed, andfurthermore, a study on a catalyst for preparing a lactam compound withexcellent selectivity and yield is also needed.

DISCLOSURE Technical Problem

While trying to solve the problem described above, the present inventorfound that a gamma-lactam compound may be prepared with excellentselectivity and yield by a novel metal complex having a specificfunctional group, thereby completing the present invention.

Therefore, an object of the present invention is to provide a novelmetal complex, a method of preparing the same, and a method of preparinga gamma-lactam compound using the same.

Another object of the present invention is to provide a lactam compoundprepared by the method of preparing a gamma-lactam compound.

Technical Solution

In one general aspect, a novel metal complex used as a catalyst forpreparing a gamma-lactam compound is provided, which is represented bythe following Chemical formula 1:

wherein

M is iridium, rhodium, ruthenium, or cobalt;

L is

X is a halogen;

R₁ to R₅ are independently of one another hydrogen or (C1-C20)alkyl; and

R₆ is a halogen, (C1-C20)alkyl, halo(C1-C20)alkyl, (C1-C20)alkoxy,(C6-C20)aryl, or (C3-C20)heteroaryl;

A is —CO— or —SO₂—;

R₇ is (C1-C20)alkyl, (C1-C20)alkoxy, (C6-C20)aryl,(C1-C20)alkyl(C6-C20)aryl, or —NR₁₁R₁₂;

R₁₁ and R₁₂ are independently of each other hydrogen or (C1-C20)alkyl;and

n is an integer of 0 to 6.

Preferably, in Chemical Formula 1 according to an exemplary embodimentof the present invention, L may be

X may be Cl or Br; R₁ to R₅ may be independently of one another(C1-C20)alkyl; R₆ may be halo(C1-C20)alkyl or (C1-C20)alkoxy; and n maybe an integer of 0 to 6.

Preferably, Chemical Formula 1 according to an exemplary embodiment ofthe present invention may be represented by the following ChemicalFormula 2:

wherein

X is a halogen;

R₆ is halo(C1-C20)alkyl or (C1-C20)alkoxy;

A is —CO— or —SO₂—;

R₇ is (C1-C20)alkyl, (C1-C20)alkoxy, (C6-C20)aryl,(C1-C20)alkyl(C6-C20)aryl, or —NR₁₁R₁₂;

R₁₁ and R₁₂ are independently of each other hydrogen or (C1-C20)alkyl;and

n is an integer of 0 or 1.

Preferably, in Chemical Formula 2 according to an exemplary embodimentof the present invention, A may be —CO—; R₆ and R₇ may be independentlyof each other (C1-C20)alkoxy; and n may be an integer of 1.

The metal complex of Chemical Formula 1 according to an exemplaryembodiment of the present invention may be used as a catalyst forpreparing a gamma-lactam compound from a dioxazol-one compound.

In another general aspect, a method of preparing a metal complexrepresented by the following Chemical Formula 1 includes: reacting ametal precursor compound of the following Chemical Formula 3A and aquinoline-based compound of the following Chemical Formula 3B in thepresence of a base to prepare the metal complex of the followingChemical Formula 1:

wherein

M is iridium, rhodium, ruthenium, or cobalt;

L is

X is independently of each other a halogen;

R₁ to R₅ are independently of one another hydrogen or (C1-C20)alkyl; and

R₆ is a halogen, (C1-C20)alkyl, halo(C1-C20)alkyl, (C1-C20)alkoxy,(C6-C20)aryl, or (C3-C20)heteroaryl;

A is —CO— or —SO₂—;

R₇ is (C1-C20)alkyl, (C1-C20)alkoxy, (C6-C20)aryl,(C1-C20)alkyl(C6-C20)aryl, or —NR₁₁R₁₂;

R₁₁ and R₁₂ are independently of each other hydrogen or (C1-C20)alkyl;and

n is an integer of 0 to 6.

Preferably, in the method of preparing the compound of Chemical Formula1 according to an exemplary embodiment of the present invention, thebase may be any one or two or more selected from NaOAc, Na₂CO₃, NaHNO₃,Cu(OAc)₂, Cu(OAc)₂.H₂O, and Net₃, and may be used at 2 to 10 mol withrespect to 1 mol of the metal precursor compound of Chemical Formula 3A.

The quinoline-based compound of Chemical Formula 3B according to anexemplary embodiment of the present invention may be used at 1.5 to 2.5mol with respect to 1 mol of the metal precursor compound of ChemicalFormula 3A.

In another general aspect, a method of preparing a gamma-lactam compoundincludes: amidating a dioxazol-one compound in the presence of a metalcomplex represented by the following Chemical Formula 1 and a base toprepare the gamma-lactam compound:

wherein

M is iridium, rhodium, ruthenium, or cobalt;

L is

X is a halogen;

R₁ to R₅ are independently of one another hydrogen or (C1-C20)alkyl; and

R₆ is a halogen, (C1-C20)alkyl, halo(C1-C20)alkyl, (C1-C20)alkoxy,(C6-C20)aryl, or (C3-C20)heteroaryl;

A is —CO— or —SO₂—;

R₇ is (C1-C20)alkyl, (C1-C20)alkoxy, (C6-C20)aryl,(C1-C20)alkyl(C6-C20)aryl, or —NR₁₁R₁₂;

R₁₁ and R₁₂ are independently of each other hydrogen or (C1-C20)alkyl;and

n is an integer of 0 to 6.

Preferably, the dioxazol-one compound according to an exemplaryembodiment of the present invention may be represented by the followingChemical Formula 4, and the gamma-lactam compound may be presented bythe following Chemical Formula 5:

wherein

R_(a1) to R_(a6) are independently of one another hydrogen,(C1-C20)alkyl, (C3-C20)cycloalkyl, (C2-C20)alkenyl, (C2-C20)alkynyl,(C1-C20)alkoxy, (C6-C20)aryl, (C3-C20)heteroaryl, or(C3-C20)heterocycloalkyl, or may be connected to an adjacent substituentto form an aromatic ring, an alicyclic ring, or spiro ring with orwithout a fused ring;

the alkyl, the cycloalkyl, the alkenyl, the alkynyl, the alkoxy, thearyl, the heteroaryl, the aromatic ring, the alicyclic ring, or thespiro ring of R_(a1) to R_(a6) may be further substituted by any one ormore substituents selected from a halogen, nitro, cyano, (C1-C20)alkyl,(C1-C20)alkenyl, (C1-C20)alkoxy, (C6-C20)aryl,(C6-C20)aryl(C1-C20)alkyl(C3-C20)heteroaryl, (C3-C20)heterocycloalkyl,and —N(R_(a11)) (R_(a12));

R_(a11) and R_(a12) are independently of each other hydrogen,(C1-C20)alkyl, or (C1-C20)alkoxycarbonyl.

Preferably, the base according to an exemplary embodiment of the methodof preparing a gamma-lactam compound of the present invention may be oneor two or more selected from NaBAr^(F) ₄ (Sodiumtetrakis[3,5-bis(trifluoromethyl)phenyl]borate), AgSbF₆ (Silverhexafluoroantimonate(V)), AgNTf₂ (Silverbis(trifluoromethanesulfonyl)imide), AgBF₄ (Silver tetrafluoroborate),AgPF₆ (Silver hexafluorophosphate), AgOTf (Silvertrifluoromethanesulfonate), and AgOAc (Silver acetate), and may be usedat 0.01 to 0.1 mol with respect to 1 mol of the dioxazol-one compound.

The metal complex of Chemical Formula 1 according to an exemplaryembodiment of the present invention may be used as a catalyst and may beused at 0.01 to 0.1 mol with respect to 1 mol of the dioxazol-onecompound.

Preferably, the amidation according to an exemplary embodiment of thepresent invention may be performed at 20 to 60° C.

Preferably, in Chemical Formula 1 according to an exemplary embodimentof the method of preparing a gamma-lactam compound of the presentinvention, M may be iridium; L may be

X may be chloro; R₁ to R₅ may be independently of one another(C1-C20)alkyl; R₆ may be (C1-C20)alkoxy; A may be —CO—; R₇ may be(C1-C20)alkoxy; and n may be an integer of 0 or 1.

Preferably, in Chemical Formulae 4 and 5 according to an exemplaryembodiment of the method of preparing a gamma-lactam compound of thepresent invention, R_(a1) to R_(a6) may be independently of one anotherhydrogen, (C1-C20)alkyl, (C3-C20)cycloalkyl, (C2-C20)alkenyl,(C2-C20)alkynyl, (C6-C20)aryl, (C3-C20)heteroaryl, or(C3-C20)heterocycloalkyl, or connected to an adjacent substituent toform an aromatic ring, an alicyclic ring, or a spiro ring with orwithout a fused ring; the alkyl, the cycloalkyl, the alkenyl, thealkynyl, the aryl, the heteroaryl, the aromatic ring, the alicyclicring, or the spiro ring of R_(a1) to R_(a6) may be further substitutedby any one or more substituents selected from a halogen, nitro, cyano,(C1-C20)alkyl, (C1-C20)alkenyl, (C1-C20)alkoxy, (C6-C20)aryl,(C6-C20)aryl(C1-C20)alkyl (C3-C20)heteroaryl, (C3-C20)heterocycloalkyl,and —N(R_(a11)) (R_(a12)); and R_(a11) and R_(a12) may be independentlyof each other (C1-C20)alkyl or (C1-C20)alkoxycarbonyl.

More preferably, R_(a1) to R_(a5) may be independently of each otherhydrogen, (C1-C20)alkyl, or (C3-C20)heterocycloalkyl; R_(a6) may beindependently of each other hydrogen, (C1-C20)alkyl, (C3-C20)cycloalkyl,(C2-C20)alkenyl, (C2-C20)alkynyl, (C6-C20)aryl, or (C3-C20)heteroaryl,or R_(a5) and R_(a6) may be connected to form a (C5-C8)spiro ring,R_(a2) and R_(a3) may be connected with (C2-C10)alkenylene to form a(C6-C12)aromatic ring, and in this case, R_(a1) and R_(a2) are absent,R_(a3) and R_(a6) may be connected to each other to form a(C3-C20)alicyclic ring with or without an aromatic ring, R_(a3) andR_(a4) and R_(a6) may be connected to each other to form a(C3-C20)alicyclic ring with or without an aromatic ring; the alkyl ofR_(a1) to R_(a6) and the alkyl, the cycloalkyl, the alkenyl, thealkynyl, the aryl, or the heteroaryl of R_(a6) may be furthersubstituted by any one or more substituents selected from a halogen,nitro, cyano, (C1-C20)alkyl, (C1-C20)alkenyl, (C1-C20)alkoxy,(C6-C20)aryl, (C6-C20)aryl(C1-C20)alkyl (C3-C20)heterocycloalkyl, and—N(R_(a11)) (R_(a12)); and R_(a11) and R_(a12) may be independently ofeach other hydrogen, (C1-C20)alkyl, or (C1-C20)alkoxycarbonyl.

Specifically, the method of preparing a gamma-lactam compound accordingto an exemplary embodiment of the present invention may includeamidating the dioxazol-one compound of the following Chemical Formula 6in the presence of the compound represented by Chemical Formula 1 andthe base to prepare a gamma-lactam compound of the following ChemicalFormula 7:

wherein

R_(a1) and R_(a3) are independently of each other hydrogen,(C1-C20)alkyl, or (C3-C20)heterocycloalkyl;

R_(a2) and R_(a5) are independently of each other hydrogen or(C1-C20)alkyl;

R_(a6) is (C1-C20)alkyl, (C3-C20)cycloalkyl, (C2-C20)alkenyl,(C2-C20)alkynyl, (C6-C20)aryl, or (C3-C20) heteroaryl;

the alkyl, the cycloalkyl, the alkenyl, the alkynyl, the aryl, and theheteroaryl of R_(a6) may be further substituted by any one or moresubstituents selected from a halogen, nitro, cyano, (C1-C20)alkyl,(C2-C20)alkenyl, (C1-C20)alkoxy, (C6-C20)aryl,(C6-C20)aryl(C1-C20)alkyl, and —N (R_(a11)) (R_(a12)); and

R_(a11) and R_(a12) are independently of each other hydrogen,(C1-C20)alkyl, or (C1-C20)alkoxycarbonyl.

Specifically, the method of preparing a gamma-lactam compound accordingto a second embodiment of the present invention may include amidatingthe dioxazol-one compound of the following Chemical Formula 8 in thepresence of the compound represented by Chemical Formula 1 and the baseto prepare a gamma-lactam compound of the following Chemical Formula 9:

wherein

ring A is a (C3-C20)alicyclic ring with or without an aromatic ring;

R_(a1) and R_(a3) are independently of each other hydrogen or(C1-C20)alkyl, and R_(a5) is hydrogen or (C2-C20)alkenyl;

the alkyl of R_(a1) and R_(a3) and the alkenyl of R_(a5) may be furthersubstituted by any one or more substituents selected from a halogen,nitro, cyano, (C1-C20)alkyl, (C2-C20)alkenyl, (C1-C20)alkoxy,(C6-C20)aryl, (C6-C20)heteroaryl, (C3-C20)heterocycloalkyl, and—N(R_(a21)) (R_(a22)); and

R_(a21) and R_(a22) are independently of each other hydrogen,(C1-C20)alkyl, or (C1-C20)alkoxycarbonyl.

Specifically, the method of preparing a gamma-lactam compound of a thirdembodiment of the present invention may include amidating thedioxazol-one compound of the following Chemical Formula 10 in thepresence of the compound represented by Chemical Formula 1 and the baseto prepare a gamma-lactam compound of the following Chemical Formula 11:

wherein

R_(a1) to R_(a3) are independently of one another hydrogen or(C1-C20)alkyl;

ring B is an alicyclic ring; and

the alkyl of R_(a1) to R_(a3) and the alicyclic ring of ring B may befurther substituted by any one or more substituents selected from ahalogen, nitro, cyano, (C1-C20)alkyl, (C2-C20)alkenyl, (C1-C20)alkoxy,(C6-C20)aryl, and (C6-C20)aryl(C1-C20)alkyl.

Specifically, the method of preparing a gamma-lactam compound of afourth embodiment of the present invention may include amidating thedioxazol-one compound of the following Chemical Formula 12 in thepresence of the compound represented by Chemical Formula 1 and the baseto prepare a gamma-lactam compound of the following Chemical Formula 13:

wherein

R_(a5) and R_(a6) are independently of each other hydrogen,(C1-C20)alkyl, or (C6-C20)aryl.

In still another general aspect, a gamma-lactam compound represented byChemical Formula 5 is provided.

Advantageous Effects

The metal complex of the present invention adopts a specific functionalgroup as a ligand in a metal, and thus, is very useful as a catalyst forpreparing a gamma-lactam compound from a dioxazol-one compound.

Therefore, the method of preparing a gamma-lactam compound using themetal complex of Chemical Formula 1 of the present invention as acatalyst may easily produce a high-purity gamma-lactam compound withhigh selectivity and yield from various dioxazol-one compounds, andthus, the prepared gamma-lactam compound may be useful as a rawmaterial, an intermediate, and the like in various fields.

BEST MODE

Hereinafter, the novel metal complex of the present invention, themethod of preparing the same, and the method of preparing a gamma-lactamcompound from a dioxazol-one compound using the same will be describedin detail, but the present invention is not limited thereto.

“Alkyl”, “alkoxy”, and a substituent containing “alkyl” described hereinrefer to a hydrocarbon radical in a linear or branched form having 1 to20 carbon atoms.

“Alkenyl” described herein is an organic radical derived from ahydrocarbon containing one or more double bonds, and

“alkynyl” described herein is an organic radical derived from ahydrocarbon containing one or more triple bonds.

“Haloalkyl” described herein refers to one or more hydrogens of thealkyl being substituted by one or more halogens, preferably fluorines.

“Cycloalkyl” described herein refers to a non-aromatic monocyclic ormulticyclic ring system having 3 to 20 carbon atoms, and a monocyclicring includes cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl,without limitation. An example of the multicyclic cycloalkyl groupincludes perhydronaphthyl, perhydroindenyl, and the like; and a bridgedmulticyclic cycloalkyl group includes adamantyl, norbornyl, and thelike.

“Heterocycloalkyl” described herein refers to a non-aromatic monocyclicor multicyclic ring system having 3 to 20 carbon atoms containing 1 to 4heteroatoms selected from B, N, O, S, P(═O), Si, and P, and

of the present invention is included therein.

“Aryl” described herein is an organic radical derived from an aromatichydrocarbon by removal of one hydrogen, including a monocyclic or fusedring system containing appropriately 4 to 7, preferably 5 or 6 ringatoms in each ring, and even including a form in which a plurality ofaryls are connected by a single bond. A specific example includesphenyl, naphthyl, biphenyl, terphenyl, anthryl, indenyl, fluorenyl,phenanthryl, triphenylenyl, pyrenyl, perylenyl, crycenyl, naphthacenyl,fluoranthenyl, and the like. Naphthyl includes 1-naphthyl and2-naphthyl, anthryl includes 1-anthryl, 2-anthryl, and 9-anthryl, andfluorenyl includes all of 1-fluorenyl, 2-fluorenyl, 3-fluorenyl,4-fluorenyl, and 9-fluorenyl.

“Heteroaryl” described herein refers to an aryl group containing 1 to 4heteroatoms selected from B, N, O, S, P(═O), Si, and P as an aromaticring backbone atom, and carbons as remaining aromatic ring backboneatoms, and is a 5- or 6-membered monocyclic heteroaryl and a multicyclicheteroaryl fused with one or more benzene rings, which may be partiallysaturated. In addition, heteroaryl in the present invention alsoincludes a form in which one or more heteroaryls are connected by asingle bond.

“Arylalkyl” described herein alone or as a portion of another grouprefers to a functional group in which one or more hydrogens of an arylgroup are substituted with alkyl, and as an example, may be methylphenylor the like.

A fused ring of an aromatic ring, an alicyclic ring, or a spiro ringcontaining a fused ring described herein may be an aromatic ring, analicyclic ring, or a spiro ring, preferably an aromatic ring oralicyclic ring, and specifically a C6-C12 aromatic ring or a C1-C12alicyclic ring, but is not limited thereto.

In addition, a “(C1-C20)alkyl group” described herein is preferably(C1-C10)alkyl, and more preferably (C1-C7)alkyl, a “(C3-C20)cycloalkylgroup” is preferably (C3-C12)cycloalkyl, a “(C3-C20)heterocycloalkylgroup” is preferably (C3-C12)heterocycloalkyl, a “(C6-C20)aryl group” ispreferably (C6-C12)aryl, and a “(C3-C30)heteroaryl group” is preferably(C3-C12)heteroaryl.

The present invention provides a novel metal complex, and the metalcomplex of the present invention may be useful as a catalyst forpreparing gamma-lactam having excellent activity and chemicalselectivity and is represented by the following Chemical Formula 1:

wherein

M is iridium, rhodium, ruthenium, or cobalt;

L is

X is a halogen;

R₁ to R₅ are independently of one another hydrogen or (C1-C20)alkyl; and

R₆ is a halogen, (C1-C20)alkyl, halo(C1-C20)alkyl, (C1-C20)alkoxy,(C6-C20)aryl, or (C3-C20)heteroaryl;

A is —CO— or —SO₂—;

R₇ is (C1-C20)alkyl, (C1-C20)alkoxy, (C6-C20)aryl,(C1-C20)alkyl(C6-C20)aryl, or —NR₁₁R₁₂;

R₁₁ and R₁₂ are independently of each other hydrogen or (C1-C20)alkyl;and

n is an integer of 0 to 6.

The novel metal complex of the present invention is a catalyst of agamma-lactam compound, has excellent catalytic activity, and amidates adioxazol-one compound under mild conditions unlike conventionalcatalysts to prepare a gamma-lactam compound with high selectivity andyield.

In terms of obtaining a gamma-lactam compound with excellent selectivityand yield, in Chemical Formula 1, L may be

More preferably, in Chemical Formula 1, L may be

X may be Cl or Br; R₁ to R₅ may be independently of one another(C1-C20)alkyl; R₆ may be halo(C1-C20)alkyl or (C1-C20)alkoxy; and n maybe an integer of 0 to 6.

More preferably, Chemical Formula 1 according to an exemplary embodimentof the present invention may be represented by the following ChemicalFormula 2:

wherein

X is a halogen;

R₆ is halo(C1-C20)alkyl or (C1-C20)alkoxy;

A is —CO— or —SO₂—;

R₇ is (C1-C20)alkyl, (C1-C20)alkoxy, (C6-C20)aryl,(C1-C20)alkyl(C6-C20)aryl, or —NR₁₁R₁₂;

R₁₁ and R₁₂ are independently of each other hydrogen or (C1-C20)alkyl;and

n is an integer of 0 or 1.

In terms of a more efficient reaction, preferably, in Chemical Formula 2according to an exemplary embodiment of the present invention, A may be—CO—.

In terms of a still more efficient reaction, preferably, in ChemicalFormula 2 according to an exemplary embodiment of the present invention,A may be —CO—; R₆ and R₇ may be independently of each other(C1-C20)alkoxy; n may be an integer of 1, and the compound representedby Chemical Formula 1 of the present invention may be used as a catalystwhich may easily produce a gamma-lactam compound from a dioxazol-onecompound.

The metal complex according to an exemplary embodiment of the presentinvention has excellent catalytic activity and significantly improvedselectivity as compared with conventional catalyst, by introducing adifferent ligand from those of the conventional catalysts, and thus, agamma-lactam compound may be easily obtained with high selectivity andyield.

Furthermore, the metal complex according to an exemplary embodiment ofthe present invention progresses an amidation reaction under mildconditions, thereby allowing mass production of a gamma-lactam compoundwhich is very useful as a raw material, an intermediate, and the like.

In addition, the present invention provides a method of preparing ametal complex represented by Chemical Formula 1 including: reacting ametal precursor compound of the following Chemical Formula 3A and aquinoline-based compound of the following Chemical Formula 3B in thepresence of a base to prepare the metal complex of Chemical Formula 1:

wherein

M is iridium, rhodium, ruthenium, or cobalt;

L is

X is independently of each other a halogen;

R₁ to R₅ are independently of one another hydrogen or (C1-C20)alkyl; and

R₆ is a halogen, (C1-C20)alkyl, halo(C1-C20)alkyl, (C1-C20)alkoxy,(C6-C20)aryl, or (C3-C20)heteroaryl;

A is —CO— or —SO₂—;

R₇ is (C1-C20)alkyl, (C1-C20)alkoxy, (C6-C20)aryl,(C1-C20)alkyl(C6-C20)aryl, or —NR₁₁R₁₂;

R₁₁ and R₁₂ are independently of each other hydrogen or (C1-C20)alkyl;and

n is an integer of 0 to 6.

Preferably, in the method of preparing the compound of Chemical Formula1 according to an exemplary embodiment of the present invention, thebase may be any one or two or more selected from NaOAc, Na₂CO₃, NaHNO₃,Cu(OAc)₂, Cu(OAc)₂.H₂O, and NEt₃, and more preferably any one or two ormore selected from NaOAc, Na₂CO₃, NaHNO₃, and Net₃, and may be used at 2to 10 mol, preferably 4 to 8 mol with respect to 1 mol of the metalprecursor compound of Chemical Formula 3A.

The quinoline-based compound of Chemical Formula 3B according to anexemplary embodiment of the present invention may be used at 1.5 to 2.5mole, preferably 1.7 to 2.3 mol with respect to 1 mol of the metalprecursor compound of Chemical Formula 3A.

In another general aspect, a method of preparing a gamma-lactam compoundincludes: amidating a dioxazol-one compound in the presence of a metalcomplex represented by the following Chemical Formula 1 and a base toprepare the gamma-lactam compound:

wherein

M is iridium, rhodium, ruthenium, or cobalt;

L is

X is a halogen;

R₁ to R₅ are independently of one another hydrogen or (C1-C20)alkyl; and

R₆ is a halogen, (C1-C20)alkyl, halo(C1-C20)alkyl, (C1-C20)alkoxy,(C6-C20)aryl, or (C3-C20)heteroaryl;

A is —CO— or —SO₂—;

R₇ is (C1-C20)alkyl, (C1-C20)alkoxy, (C6-C20)aryl,(C1-C20)alkyl(C6-C20)aryl, or —NR₁₁R₁₂;

R₁₁ and R₁₂ are independently of each other hydrogen or (C1-C20)alkyl;and

n is an integer of 0 to 6.

Preferably, the metal complex according to an exemplary embodiment ofthe present invention may be represented by the following ChemicalFormula 1-1:

wherein M, X, R₁ to R₇, A, and n are as defined in Chemical Formula 1.

Preferably, the dioxazol-one compound according to an exemplaryembodiment of the present invention may be represented by the followingChemical Formula 4, and the gamma-lactam compound may be presented bythe following Chemical Formula 5:

wherein

R_(a1) to R_(a6) are independently of one another hydrogen,(C1-C20)alkyl, (C3-C20)cycloalkyl, (C2-C20)alkenyl, (C2-C20)alkynyl,(C1-C20)alkoxy, (C6-C20)aryl, (C3-C20)heteroaryl, or(C3-C20)heterocycloalkyl, or may be connected to an adjacent substituentto form an aromatic ring, an alicyclic ring, or spiro ring with orwithout a fused ring;

the alkyl, the cycloalkyl, the alkenyl, the alkynyl, the alkoxy, thearyl, the heteroaryl, the aromatic ring, the alicyclic ring, or thespiro ring of R_(a1) to R_(a6) may be further substituted by any one ormore substituents selected from a halogen, nitro, cyano, (C1-C20)alkyl,(C1-C20)alkenyl, (C1-C20)alkoxy, (C6-C20)aryl,(C6-C20)aryl(C1-C20)alkyl, (C3-C20)heteroaryl, (C3-C20)heterocycloalkyl,and —N(R_(a11)) (R_(a12)); and

R_(a11) and R_(a12) are independently of each other hydrogen,(C1-C20)alkyl, or (C1-C20)alkoxycarbonyl.

The method of preparing a gamma-lactam compound of the present inventionmay easily produce a gamma-lactam compound unlike unstable conventionalmethods, by introducing a dioxazol-one compound which is a specificstarting material as a starting material instead of carbonylnitreneswhich have been used as a conventional starting material, andfurthermore, may produce a gamma-lactam compound with high selectivityunder mild conditions.

Besides, the method of preparing a gamma-lactam compound of the presentinvention adopts a quinoline amine compound which is not aconventionally used catalyst but a specific ligand, thereby easilypreparing a gamma-lactam compound with high selectivity and yield undermild conditions.

Preferably, the base according to an exemplary embodiment of the methodof preparing a gamma-lactam compound of the present invention may be oneor two or more selected from NaBAr^(F) ₄ (sodiumtetrakis[3,5-bis(trifluoromethyl)phenyl]borate), AgSbF₆ (silverhexafluoroantimonate(V)), AgNTf₂ (silverbis(trifluoromethanesulfonyl)imide), AgBF₄ (silver tetrafluoroborate),AgPF₆ (silver hexafluorophosphate), AgOTf (silvertrifluoromethanesulfonate), and AgOAc (silver acetate), preferably oneor two or more selected from NaBAr^(F) ₄ (sodiumtetrakis[3,5-bis(trifluoromethyl)phenyl]borate), AgSbF₆, AgNTf₂, andAgBF₄, and may be used at 0.01 to 0.1 mol, preferably 0.01 to 0.07 molwith respect to 1 mol of the dioxazol-one compound.

The metal complex according to an exemplary embodiment of the presentinvention is used as a catalyst, and may be used at 0.01 to 0.1 mol,preferably 0.01 to 0.07 mol with respect to 1 mol of the dioxazol-onecompound.

Preferably, amidation according to an exemplary embodiment of thepresent invention may be performed by stirring at 20 to 60° C.,preferably 30 to 50° C. for 8 to 24 hours, preferably 10 to 15 hours.

In the method of preparing a gamma-lactam compound according to anexemplary embodiment of the present invention, amidation may beperformed under an organic solvent, and it is not necessary to limit theorganic solvent as long as it dissolves the reaction material. As theorganic solvent according to an exemplary embodiment of the presentinvention, one or more selected from acetonitrile, dichloromethane,dichloroethane, nitromethane, toluene, and benzene may be used, andconsidering solubility and ease of removal of the reactant, one or moreselected from dichloromethane, dichloroethane, and acetonitrile may beused as a solvent.

Preferably, in Chemical Formula 1 according to an exemplary embodimentof the method of preparing a gamma-lactam compound of the presentinvention, M may be iridium; L may be

X may be chloro; R₁ to R₅ may be independently of one another(C1-C20)alkyl; R₆ may be (C1-C20)alkoxy; A may be —CO—; R₇ may be(C1-C20)alkoxy; and n may be an integer of 0 or 1.

Preferably, in Chemical Formulae 4 and 5 according to an exemplaryembodiment of the method of preparing a gamma-lactam compound of thepresent invention, R_(a1) to R_(a5) may be independently of each otherhydrogen, (C1-C20)alkyl, or (C3-C20)heterocycloalkyl; R_(a6) may beindependently of each other hydrogen, (C1-C20)alkyl, (C3-C20)cycloalkyl,(C2-C20)alkenyl, (C2-C20)alkynyl, (C6-C20)aryl, or (C3-C20)heteroaryl,or R_(a5) and R_(a6) may be connected to form a (C5-C8)spiro ring,R_(a2) and R_(a3) may be connected with (C2-C10)alkenylene to form a(C6-C12)aromatic ring, and in this case, R_(a1) and R_(a2) are absent,R_(a3) and R_(a6) may be connected to each other to form a(C3-C20)alicyclic ring with or without an aromatic ring, R_(a3) andR_(a4) and R_(a6) may be connected to each other to form a(C3-C20)alicyclic ring with or without an aromatic ring; the alkyl ofR_(a1) to R_(a5), and the alkyl, the cycloalkyl, the alkenyl, thealkynyl, the aryl, or the heteroaryl of R_(a6) may be furthersubstituted by any one or more substituents selected from a halogen,nitro, cyano, (C1-C20)alkyl, (C1-C20)alkenyl, (C1-C20)alkoxy,(C6-C20)aryl, (C6-C20)aryl(C1-C20)alkyl (C3-C20)heterocycloalkyl, and—N(R_(a11)) (R_(a12)); and R_(a11) and R_(a12) may be independently ofeach other hydrogen, (C1-C20)alkyl, or (C1-C20)alkoxycarbonyl.

Preferably, a first embodiment of the method of preparing a gamma-lactamcompound of the present invention may include amidating the dioxazol-onecompound of the following Chemical Formula 6 in the presence of thecompound represented by Chemical Formula 1 and the base to prepare agamma-lactam compound of the following Chemical Formula 7:

wherein

R_(a1) and R_(a3) are independently of each other hydrogen,(C1-C20)alkyl, or (C3-C20)heterocycloalkyl;

R_(a2) and R_(a5) are independently of each other hydrogen or(C1-C20)alkyl;

R_(a6) is (C1-C20)alkyl, (C3-C20)cycloalkyl, (C2-C20)alkenyl,(C2-C20)alkynyl, (C6-C20)aryl, or (C3-C20) heteroaryl;

the alkyl, the cycloalkyl, the alkenyl, the alkynyl, the aryl, and theheteroaryl of R_(a6) may be further substituted by any one or moresubstituents selected from a halogen, nitro, cyano, (C1-C20)alkyl,(C2-C20)alkenyl, (C1-C20)alkoxy, (C6-C20)aryl,(C6-C20)aryl(C1-C20)alkyl, and —N (R_(a11)) (R_(a12)); and

R_(a11) and R_(a12) are independently of each other hydrogen,(C1-C20)alkyl, or (C1-C20)alkoxycarbonyl.

Preferably, a second embodiment of the gamma-lactam compound of thepresent invention may be prepared by including amidating thedioxazol-one compound of the following Chemical Formula 8 in thepresence of the compound represented by Chemical Formula 1 and the baseto prepare a gamma-lactam compound of the following Chemical Formula 9:

wherein

ring A is a (C3-C20)alicyclic ring with or without an aromatic ring;

R_(a1) and R_(a3) are independently of each other hydrogen or(C1-C20)alkyl, and R_(a5) is hydrogen or (C2-C20)alkenyl;

the alkyl of R_(a1) and R_(a3) and the alkenyl of R_(a5) may be furthersubstituted by any one or more substituents selected from a halogen,nitro, cyano, (C1-C20)alkyl, (C2-C20)alkenyl, (C1-C20)alkoxy,(C6-C20)aryl, (C6-C20)heteroaryl, (C3-C20)heterocycloalkyl, and—N(R_(a21)) (R_(a22)); and

R_(a21) and R_(a22) are independently of each other hydrogen,(C1-C20)alkyl, or (C1-C20)alkoxycarbonyl.

Preferably, a third embodiment of the gamma-lactam compound of thepresent invention may be prepared by including amidating thedioxazol-one compound of the following Chemical Formula 10 in thepresence of the compound represented by Chemical Formula 1 and the baseto prepare a gamma-lactam compound of the following Chemical Formula 11:

wherein

R_(a1) to R_(a3) are independently of one another hydrogen or(C1-C20)alkyl;

ring B is an alicyclic ring; and

the alkyl of R_(a1) to R_(a3) and the alicyclic ring of ring B may befurther substituted by any one or more substituents selected from ahalogen, nitro, cyano, (C1-C20)alkyl, (C2-C20)alkenyl, (C1-C20)alkoxy,(C6-C20)aryl, and (C6-C20)aryl(C1-C20)alkyl.

Preferably, a fourth embodiment of the gamma-lactam compound of thepresent invention may be prepared by including amidating thedioxazol-one compound of the following Chemical Formula 12 in thepresence of the compound represented by Chemical Formula 1 and the baseto prepare a gamma-lactam compound of the following Chemical Formula 13:

wherein

R_(a5) and R_(a6) are independently of each other hydrogen,(C1-C20)alkyl, or (C6-C20)aryl.

In addition, the present invention provides a gamma-lactam compoundrepresented by Chemical Formula 5.

Hereinafter, the constitution of the present invention will be describedin detail by the Examples, and the following Examples are for betterunderstanding of the present invention, but the scope of the presentinvention is not limited thereto.

Preparation Example I: Preparation of Quinoline Ligand

Method 1.

Methyl carbamate (1.1 mmol, 1.1 equivalents to quinoline N-oxide, 82.5mg), trichloroisocyanuric acid (TCCA, 86 mg, 0.36 mmol, 37 mol %), andMeOH (2 mL) were added to a vial and the mixture was stirred at 25° C.for 1 hour. Quinoline N-oxide (1.0 mmol), [RhCp*Cl₂]2 (Cp*:pentamethylcyclopentadienyl) (12.5 mg, 0.02 mmol, 2 mol %), AgNTf₂ (31mg, 0.08 mmol, 8 mol %), AgOAc (183.5 mg, 1.1 mmol), and MeOH (1 mL)were added thereto again and the mixture was stirred at 50° C. for 12hours. After the reaction was completed, the reaction mixture wasfiltered with celite (dichloromethane (15 mL×3)). After the solvent wasremoved by distillation under reduced pressure, separation andpurification were performed by column chromatography(dichloromethane/methanol=30:1 to 10:1) to obtain compound 1-1 as atitle compound.

Compound 1-1 was dissolved in THE (15 mL), an aqueous 30% NH₅Cl solution(15 mL) and zinc dust (0.59 g, 9 mmol) were added thereto, and themixture was stirred at room temperature for 1 hour. Thereafter, H₂O (50mL) was added to the reaction mixture, extraction was performed withEtOAc (50 mL×3), and drying was performed with MgSO₄ to remove residualmoisture. After the solvent was removed by distillation under reducedpressure, separation and purification were performed by columnchromatography (eluent: n-hexane/EtOAc=4:1 to 1:1) to prepare quinolineligand compound 1-2.

The following quinoline ligand compound was prepared in the same manneras in the above, except that a starting material having differentsubstituents was used.

[Preparation Example 1] Preparation of methyl quinolin-8-ylcarbamate

White solid (0.12 g, 61%, 2 steps yield); m.p. 65-67° C.; ¹H NMR (600MHz, CDCl₃) δ 9.21 (s, 1H), 8.78 (d, J=4.2 Hz, 1H), 8.42 (d, J=6.3 Hz,1H), 8.13 (dd, J=8.2, 1.5 Hz, 1H), 7.53 (t, J=8.0 Hz, 1H), 7.47-7.40 (m,2H), 3.85 (s, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 154.1, 148.1, 138.2,136.2, 134.7, 128.0, 127.3, 121.6, 120.6, 114.5, 52.3; IR (cm⁻¹) 3358,1728, 1524, 1486, 1200; HRMS (EI) m/z calcd. for C₁₁H₁₀N₂O₂[M]⁺:202.0742, found: 202.0741.

[Preparation Example 2] Preparation of methyl(4-methoxyquinolin-8-yl)carbamate

White solid (0.13 g, 56%, 2 steps yield); m.p. 151-153° C.; ¹H NMR (600MHz, CDCl₃) δ 9.21 (s, 1H), 8.63 (d, J=5.2 Hz, 1H), 8.41 (d, J=6.6 Hz,1H), 7.80 (d, J=9.6 Hz, 1H), 7.47 (t, J=8.1 Hz, 1H), 6.77 (d, J=5.2 Hz,1H), 4.05 (s, 3H), 3.84 (s, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 162.5,154.1, 149.1, 139.1, 134.4, 126.1, 121.0, 114.9, 114.6, 100.6, 55.8,52.2; IR (cm⁻¹) 3366, 1719, 1527, 1411, 1232, 1023, 753, 634; HRMS (EI)m/z calcd. for C₁₂H₁₂N₂O₃ [M]⁺: 232.0848, found: 232.0845.

[Preparation Example 3] Preparation of methyl(6-methoxyquinolin-8-yl)carbamate

White solid (0.18 g, 76%, 2 steps yield); m.p. 82-84° C.; ¹H NMR (600MHz, CDCl₃) δ 9.17 (s, 1H), 8.62 (dd, J=4.1, 1.4 Hz, 1H), 8.14 (s, 1H),8.01 (d, J=8.2 Hz, 1H), 7.38 (dd, J=8.2, 4.2 Hz, 1H), 6.74 (d, J=2.5 Hz,1H), 3.92 (s, 3H), 3.85 (s, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 158.5,153.9, 145.5, 135.7, 134.9, 129.0, 122.0, 110.0, 107.1, 98.8, 55.5,52.3; IR (cm⁻¹) 3364, 1728, 1529, 1221; HRMS (EI) m/z calcd. forC₁₂H₁₂N₂O₃ [M]⁺: 232.0848, found: 232.0851.

[Preparation Example 4] Preparation of methyl(5-methoxyquinolin-8-yl)carbamate

8-amino-5-methoxyquinoline (0.87 g, 5 mmol) and sodium bicarbonate (0.46g, 5.5 mmol) were added to dried THE (20 mL) and cooled to 0° C. usingan ice-bath, methyl chloroformate (0.42 mL, 5.5 mmol) was slowly added,and the reaction mixture was stirred at room temperature for 12 hours.The reaction mixture was filtered with celite (dichloromethane (15mL×3)), distilled under reduced pressure, and separated and purified bycolumn chromatography (eluent: n-hexane/EtOAc=4:1) to obtain quinolineligand compound 1-3.

Light brown solid (0.95 g, 84%); m.p. 118-120° C.; ¹H NMR (600 MHz,CD₂Cl₂) δ 8.86 (s, 1H), 8.78 (d, J=4.0 Hz, 1H), 8.54 (d, J=9.8 Hz, 1H),8.26 (d, J=7.0 Hz, 1H), 7.43 (dd, J=8.4, 4.2 Hz, 1H), 6.85 (d, J=8.5 Hz,1H), 3.96 (s, 3H), 3.78 (s, 3H); ¹³C NMR (150 MHz, CD₂Cl₂) δ 154.0,149.7, 148.7, 138.8, 131.0, 128.0, 120.8, 120.5, 114.3, 104.3, 55.7,52.0; IR (cm⁻¹) 3366, 1719, 1524, 1493, 1221, 1086, 837, 604; HRMS (EI)m/z calcd. for C₁₂H₁₂N₂O₃ [M]⁺: 232.0848, found: 232.0848.

[Preparation Example 5] Preparation of methyl(5-(trifluoromethyl)quinolin-8-yl)carbamate

After methyl quinolin-8-ylcarbamate (404 mg, 2 mmol) was dissolved in1,2-dichloroethane (20 mL) in a 100 mL round flask, CuCl (9.9 mg, 0.1mmol, 5.0 mol %) and 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (632mg, 2 mmol) were added thereto and the mixture was stirred at 25° C. for18 hours. After the reaction was completed, the solvent was removed, andseparation and purification were performed by column chromatography(n-hexane/ethyl acetate=10/1) to obtain desired quinoline ligandcompound 1-4.

White solid (147 mg, 27%); m.p. 114-116° C.; ¹H NMR (600 MHz, CDCl₃) δ9.41 (s, 1H), 8.85 (d, J=4.0 Hz, 1H), 8.48 (d, J=8.6 Hz, 1H), 8.44 (d,J=8.0 Hz, 1H), 7.90 (d, J=8.2 Hz, 1H), 7.57 (dd, J=8.6, 4.1 Hz, 1H),3.88 (s, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 153.8, 148.5, 138.4, 137.9,133.0 (q, J=2.4 Hz), 126.4 (q, J=5.8 Hz), 124.3 (q, J=272.4 Hz), 124.3,122.8, 118.7 (q, J=31.0 Hz), 112.1, 52.6; ¹⁹F NMR (564 MHz, CDCl₃) δ−58.70 (s); IR (cm⁻¹) 3370, 1735, 1529, 1316, 1086, 858; HRMS (EI) m/zcalcd. for C₁₂H₉F₃N₂O₂ [M]⁺: 270.0616, found: 270.0613.

Example I: Preparation of Metal Complex [Examples 1 to 4] Preparation ofMetal Complexes C to F

[IrCp*Cl₂]₂ (Cp*: pentamethylcyclopentadienyl) (0.20 g, 0.25 mmol), aquinoline ligand compound (0.50 mmol), sodium acetate (0.12 g, 1.5mmol), and dichloromethane (10 mL) were added to a vial and the mixturewas stirred at room temperature for 12 hours. After the reaction wascompleted, the reaction mixture was filtered with celite(dichloromethane (15 mL×3)), the solvent was removed by distillationunder reduced pressure, and separation and purification were performedby column chromatography (n-hexane/acetone=2:1 to 1:1) to prepare metalcatalysts C to F.

[Example 1] 8-(N-Tosyl)aminoquinoline bound Cp*-iridium complex (metalcatalyst C)

Orange solid (0.22 g, 66%); ¹H NMR (600 MHz, CDCl₃) δ 8.66 (d, J=5.0 Hz,1H), 8.10 (d, J=8.3 Hz, 2H), 7.98 (d, J=8.3 Hz, 1H), 7.39 (dd, J=8.3,5.1 Hz, 1H), 7.34 (d, J=8.0 Hz, 1H), 7.22 (t, J=8.0 Hz, 1H), 7.04 (d,J=8.1 Hz, 2H), 6.89 (d, J=8.0 Hz, 1H), 2.22 (s, 3H), 1.68 (s, 15H); ¹³CNMR (150 MHz, CDCl₃) δ 149.3, 147.3, 145.2, 141.3, 138.0, 137.4, 129.7,129.0, 128.9, 128.7, 122.2, 118.0, 116.6, 87.3 (Cp*), 21.3, 9.3 (Cp*);IR (cm⁻¹) 3051, 1462, 1375, 1299, 1138, 869, 655, 572; HRMS (EI) m/zcalcd. for C₂₆H₂₈ClIrN₂O₂S [M]⁺: 660.1189, found: 660.1187.

[Example 2] 8-(N-Benzylamino)quinoline bound Cp*-iridium complex (metalcatalyst D)

Orange solid (0.22 g, 70%); ¹H NMR (400 MHz, CDCl₃) δ 8.67 (d, J=4.9 Hz,1H), 8.03 (d, J=8.3 Hz, 1H), 7.91 (d, J=7.7 Hz, 2H), 7.38 (d, J=7.8 Hz,2H), 7.28-7.22 (m, 3H), 7.19 (t, J=8.0 Hz, 1H), 6.98 (d, J=7.9 Hz, 1H),1.45 (s, 15H); ¹³C NMR (150 MHz, CDCl₃) δ 177.6, 151.7, 148.8, 145.8,140.2, 137.8, 130.0, 129.7, 129.4, 128.8, 127.7, 122.5, 122.0, 117.1,86.9 (Cp*), 8.9 (Cp*); IR (cm⁻¹) 2914, 1599, 1501, 1373, 1316; HRMS (EI)m/z calcd. for C₂₆H₂₆ClIrN₂O [M]⁺: 610.1363, found: 610.1367.

[Example 3] 8-(N-Acetylamino)quinoline bound Cp*-iridium complex (metalcatalyst E)

Yellow solid (0.19 g, 68%); ¹H NMR (600 MHz, CDCl₃) δ 8.84 (d, J=8.0 Hz,1H), 8.59 (d, J=4.9 Hz, 1H), 8.05 (d, J=8.2 Hz, 1H), 7.50 (t, J=8.0 Hz,1H), 7.38 (dd, J=8.2, 5.0 Hz, 1H), 7.14 (d, J=8.0 Hz, 1H), 2.59 (s, 3H),1.50 (s, 15H); ¹³C NMR (150 MHz, CDCl₃) δ 177.1, 150.2, 149.6, 146.3,138.0, 129.8, 128.9, 123.3, 121.9, 118.4, 86.6 (Cp*), 28.8, 8.7 (Cp*);IR (cm⁻¹)1602, 1492, 1365, 1315, 829, 762; HRMS (EI) m/z calcd. forC₂₁H₂₄ClIrN₂O [M]⁺: 548.1206, found: 548.1204.

[Example 4] 8-[N-(tert-Butyloxycarbonyl) amino] quinoline boundCp*-iridium complex (metal catalyst F)

Orange solid (0.21 g, 70%); ¹H NMR (600 MHz, CDCl₃) δ 8.61-8.57 (m, 1H),8.35 (d, J=8.0 Hz, 1H), 8.01-7.95 (m, 1H), 7.47 (t, J=8.0 Hz, 1H), 7.34(dd, J=8.3, 5.0 Hz, 1H), 7.02 (d, J=7.9 Hz, 1H), 1.56 (s, 24H); ¹³C NMR(150 MHz, CDCl₃) δ 158.6, 151.4, 149.4, 146.4, 137.6, 129.4, 129.1,122.4, 121.8, 116.5, 86.2 (Cp*), 78.6, 28.9, 8.9 (Cp*); IR (cm⁻¹) 2970,1652, 1447, 1296, 1154, 1108, 993, 761; HRMS (EI) m/z calcd. forC₂₄H₃₀ClIrN₂O₂[M]⁺: 606.1625, found: 606.1627.

[Examples 5 to 10] Preparation of metal complexes G to L

[IrCp*Cl₂]₂ (Cp*: pentamethylcyclopentadienyl) (0.20 g, 0.25 mmol), aquinoline ligand compound (0.50 mmol), sodium carbonate (0.16 g, 1.50mmol), and dichloromethane (10 mL) were added to a vial and the mixturewas stirred at room temperature for 12 hours. After the reaction wascompleted, the reactants were filtered with celite (dichloromethane (15mL×3)), the solvent was removed by distillation under reduced pressure,and separation and purification were performed by column chromatography(n-hexane/acetone=2:1 to 1:1) to prepare metal catalysts G to L.

[Example 5] 8-[N-(Methyloxycarbonyl)amino]quinoline bound Cp*-iridiumcomplex (metal catalyst G)

Yellow solid (0.24 g, 84%); ¹H NMR (600 MHz, CDCl₃) δ 8.64 (dd, J=10.2,6.6 Hz, 2H), 8.05 (d, J=8.2 Hz, 1H), 7.51 (t, J=8.0 Hz, 1H), 7.34 (dd,J=8.2, 5.1 Hz, 1H), 7.09 (d, J=7.9 Hz, 1H), 3.75 (s, 3H), 1.57 (s, 15H);¹³C NMR (150 MHz, CDCl₃) δ 159.7, 150.7, 148.9, 145.8, 137.8, 129.7,129.5, 121.8, 121.7, 117.1, 86.6 (Cp*), 52.6, 8.9 (Cp*); IR (cm⁻¹) 1645,1500, 1376, 1302, 1174, 1030, 831; HRMS (EI) m/z calcd. forC₂₁H₂₄ClIrN₂O₂[M]⁺: 564.1156, found: 564.1157.

[Example 6] 8-[N—(N,N-Dimethylaminocarbonyl)amino]quinoline boundCp*-iridium complex (metal catalyst H)

Red solid (0.15 g, 51%); ¹H NMR (400 MHz, CDCl₃) δ 8.47 (d, J=5.0 Hz,1H), 7.92 (d, J=8.4 Hz, 1H), 7.34-7.28 (m, 2H), 6.93 (d, J=8.0 Hz, 1H),6.68 (d, J=7.9 Hz, 1H), 3.17 (s, 6H), 1.62 (s, 15H); ¹³C NMR (150 MHz,CDCl₃, two carbons merged to others) δ 166.5, 154.8, 147.0, 145.0,137.7, 130.5, 129.9, 121.7, 115.6, 111.6, 86.0 (Cp*), 8.4 (Cp*); IR(cm⁻¹) 2910, 1622, 1460, 1358, 1327, 1150, 811, 772; HRMS (EI) m/zcalcd. for C₂₂H₂₇ClIrN₃O [M]⁺: 577.1472, found: 577.1475.

[Example 7] 8-[N-(Methyloxycarbonyl)amino]-5-trifluoromethyl quinolinebound Cp*-iridium complex (metal catalyst I)

Orange solid (0.22 g, 70%); ¹H NMR (600 MHz, CDCl₃) δ 8.73 (d, J=5.1 Hz,1H), 8.61 (d, J=8.6 Hz, 1H), 8.37 (d, J=8.7 Hz, 1H), 7.86 (d, J=8.7 Hz,1H), 7.49 (dd, J=8.7, 5.1 Hz, 1H), 3.77 (s, 3H), 1.57 (s, 15H); ¹³C NMR(150 MHz, CDCl₃) δ 159.6, 154.4, 149.6, 145.8, 134.6, 128.7 (q, J=5.2Hz), 126.2, 124.2 (q, J=271.9 Hz), 123.0, 119.0, 115.0 (q, J=31.4 Hz),86.9 (Cp*), 52.9, 8.9 (Cp*); ¹⁹F NMR (564 MHz, CDCl₃) δ −58.08 (s); IR(cm⁻¹) 1660, 1511, 1314, 1285, 1133, 1098, 847; HRMS (EI) m/z calcd. forC₂₂H₂₃ClF₃IrN₂O₂[M]⁺: 632.1029, found: 632.1031.

[Example 8] 4-Methoxy-8-[N-(methyloxycarbonyl)amino]quinoline boundCp*-iridium complex (metal catalyst J)

Yellow solid (0.24 g, 80%); ¹H NMR (600 MHz, CDCl₃) δ 8.65 (d, J=8.0 Hz,1H), 8.52 (d, J=6.0 Hz, 1H), 7.43 (t, J=8.1 Hz, 1H), 7.33 (d, J=8.8 Hz,1H), 6.50 (d, J=6.0 Hz, 1H), 3.80 (s, 3H), 3.75 (s, 3H), 1.55 (s, 15H);¹³C NMR (150 MHz, CDCl₃) δ 163.5, 159.8, 150.4, 150.3, 146.0, 128.4,121.9, 121.7, 111.4, 101.7, 86.1 (Cp*), 56.1, 52.6, 8.9 (Cp*); IR (cm⁻¹)1641, 1513, 1410, 1308, 1198, 1028, 750; HRMS (EI) m/z calcd. forC₂₂H₂₆ClIrN₂O₃[M]⁺: 594.1261, found: 594.1261.

[Example 9] 5-Methoxy-8-[N-(methyloxycarbonyl)amino]quinoline boundCp*-iridium complex (metal catalyst K)

Orange solid (0.27 g, 91%); ¹H NMR (600 MHz, CDCl₃) δ 8.66 (d, J=4.8 Hz,1H), 8.59 (d, J=8.8 Hz, 1H), 8.46 (d, J=8.4 Hz, 1H), 7.35 (dd, J=8.3,5.0 Hz, 1H), 6.95 (d, J=8.8 Hz, 1H), 3.96 (s, 3H), 3.73 (s, 3H), 1.56(s, 15H); ¹³C NMR (150 MHz, CDCl₃) δ 159.6, 149.6, 147.5, 145.9, 143.9,132.9, 121.2, 120.9, 120.8, 107.2, 86.4 (Cp*), 56.2, 52.5, 8.9 (Cp*); IR(cm⁻¹) 1645, 1571, 1470, 1378, 1323, 1295, 1093; HRMS (EI) m/z calcd.for C₂₂H₂₆ClIrN₂O₃ [M]⁺: 594.1261, found: 594.1260.

[Example 10] 6-Methoxy-8-[N-(methyloxycarbonyl)amino]quinoline boundCp*-iridium complex (metal catalyst L)

Yellow solid (0.24 g, 81%); ¹H NMR (600 MHz, CDCl₃) δ 8.45 (d, J=5.0 Hz,1H), 8.39 (d, J=2.3 Hz, 1H), 7.90 (d, J=8.3 Hz, 1H), 7.29-7.24 (m, 1H),6.51 (d, J=2.2 Hz, 1H), 3.89 (s, 3H), 3.75 (s, 3H), 1.56 (s, 15H); ¹³CNMR (150 MHz, CDCl₃) δ 160.9, 159.7, 151.8, 55.7, 52.7, 8.9 (Cp*); IR(cm⁻¹) 1637, 1572, 1497, 1378, 1296, 1258, 1054, 724; HRMS (EI) m/zcalcd. for C₂₂H₂₆ClIrN₂O₃[M]⁺: 594.1261, found: 594.1260.

[Example 11] Preparation of Metal Complex M

[Ru(p-cymene)Cl₂]₂ (122 mg, 0.20 mmol), methyl(5-methoxyquinolin-8-yl)carbamate (92 mg, 0.40 mmol), sodium carbonate(126 mg, 1.50 mmol), and dichloromethane (10 mL) were added to a vialand the mixture was stirred at room temperature for 12 hours. After thereaction was completed, the reaction mixture was filtered with celiteand washed (dichloromethane (15 mL×3)), the solvent was removed underreduced pressure, and the residue was separated and purified by columnchromatography (n-hexane/acetone=2:1 to 1:1) to prepare the followingmetal catalyst M.

5-Methoxy-8-[N-(methyloxycarbonyl) amino] quinoline boundp-cymene-ruthenium complex (metal catalyst M)

Orange solid (150 mg, 75%); ¹H NMR (600 MHz, CDCl₃) δ 9.07 (d, J=4.8 Hz,1H), 8.70 (d, J=8.8 Hz, 1H), 8.48 (d, J=8.2 Hz, 1H), 7.32 (dd, J=8.2,5.1 Hz, 1H), 6.87 (d, J=8.8 Hz, 1H), 5.71 (d, J=5.9 Hz, 1H), 5.31 (d,J=5.9 Hz, 1H), 5.24 (t, J=6.2 Hz, 2H), 3.91 (s, 3H), 3.80 (s, 3H), 2.46(hept, J=7.0 Hz, 1H), 2.29 (s, 3H), 0.96 (d, J=6.9 Hz, 3H), 0.87 (d,J=6.8 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 160.8, 151.4, 146.6, 145.0,143.6, 132.6, 120.8, 120.7, 120.6, 107.5, 103.1, 100.1, 86.2, 84.5,82.9, 82.7, 56.2, 52.1, 30.8, 22.2, 22.0, 19.0.

[Example 12] Preparation of Metal Complex N

[RhCp*Cl₂]₂ (77 mg, 0.125 mmol), methyl(5-methoxyquinolin-8-yl)carbamate (58 mg, 0.25 mmol), sodium carbonate(79.5 mg, 0.75 mmol), and dichloromethane (5 mL) were added to a vialand the mixture was stirred at room temperature for 12 hours. After thereaction was completed, the reaction mixture was filtered with celiteand washed (dichloromethane (15 mL×3)), the solvent was removed underreduced pressure, and recrystallization was performed with a smallamount of acetone at −30° C. to prepare the following metal catalyst N.

5-Methoxy-8-{N-(methyloxycarbonyl)amino}quinoline bound Cp*-rhodiumcomplex (metal catalyst N)

Orange solid (90 mg, 71%); ¹H NMR (600 MHz, CDCl₃) δ 8.71 (d, J=4.9 Hz,1H), 8.60 (d, J=8.7 Hz, 1H), 8.51 (d, J=8.3 Hz, 1H), 7.39 (dd, J=8.4,5.0 Hz, 1H), 6.89 (d, J=8.7 Hz, 1H), 3.93 (s, 3H), 3.73 (s, 3H), 1.54(s, 15H); ¹³C NMR (150 MHz, CDCl₃) δ 160.3, 150.0, 146.9, 145.5, 143.3,132.9, 121.1, 120.9, 120.7, 107.4, 94.5, 94.4, 56.2, 52.0, 8.9.

[Example 13] Preparation of Metal Complex O

[CoCp*Cl₂]₂ (66 mg, 0.125 mmol), methyl(5-methoxyquinolin-8-yl)carbamate (58 mg, 0.25 mmol), potassiumhydroxide (42 mg, 0.75 mmol), and dichloromethane (5 mL) were added to avial and the mixture was stirred at room temperature for 12 hours. Afterthe reaction was completed, the reaction mixture was filtered withcelite and washed (dichloromethane (15 mL×3)), the solvent was removedunder reduced pressure, and recrystallization was performed with a smallamount of acetone at −30° C. to prepare the following metal catalyst O.

5-Methoxy-8-{N-(methyloxycarbonyl)amino}quinoline bound Cp*-cobaltcomplex (metal complex O)

Green solid (34 mg, 30%); ¹H NMR (600 MHz, CD₂Cl₂) δ 9.24 (dd, J=5.1,1.4 Hz, 1H), 8.53 (dd, J=8.4, 1.4 Hz, 1H), 8.36 (d, J=8.6 Hz, 1H), 7.56(dd, J=8.4, 5.1 Hz, 1H), 6.88 (d, J=8.6 Hz, 1H), 3.95 (s, 3H), 3.73 (s,3H), 1.10 (s, 15H).

[Comparative Example 1] Preparation of Metal Complex A

[IrCp*Cl₂]₂ (0.4106 g, 0.5154 mmol), 2-(2′-pyridyl)-2-propanol (0.1420g, 1.036 mmol), sodium bicarbonate (0.345 g, 4.11 mmol), and acetone (50mL) were added to a vial and the mixture was stirred at room temperaturefor 2 hours. After the reaction was completed, the reactants werefiltered with celite (dichloromethane (15 mL×3)), the solvent wasremoved by distillation under reduced pressure, and separation andpurification were performed by column chromatography(n-hexane/acetone=2:1 to 1:1) to prepare metal catalyst A.

Yellow solid (0.416 g, 81%); ¹H NMR (400 MHz, MeOD) δ 8.69 (dt, J=5.2,1.3 Hz, 1H), 7.88 (td, J=7.9, 1.5 Hz, 1H), 7.46-7.31 (m, 2H), 1.67 (s,15H), 1.46 (s, 6H); ¹³C NMR (150 MHz, MeOD) δ 177.34, 150.97, 139.53,125.54, 122.95, 85.97, 84.74, 33.67, 9.01.

[Comparative Example 2] Preparation of Metal Complex B

[IrCp*Cl₂]₂ (0.20 g, 0.25 mmol), quinolin-8-ol (72.6 mg, 0.50 mmol),sodium carbonate (0.21 g, 2.0 mmol), and acetone (10 mL) were added to avial and the mixture was stirred at room temperature for 12 hours. Afterthe reaction was completed, the reactants were filtered with celite(dichloromethane (15 mL×3)), the solvent was removed by distillationunder reduced pressure, and separation and purification were performedby column chromatography (n-hexane/acetone=2:1 to 1:1) to prepare metalcatalyst B.

8-Hydroxyquinoline bound Cp*-iridium complex (metal catalyst B)

Orange solid (0.20 g, 80%); ¹H NMR (600 MHz, CDCl₃) δ 8.54 (d, J=4.9 Hz,1H), 8.03 (d, J=8.3 Hz, 1H), 7.36 (t, J=7.9 Hz, 1H), 7.30 (dd, J=8.3,4.9 Hz, 1H), 7.00 (d, J=7.9 Hz, 1H), 6.78 (d, J=7.9 Hz, 1H), 1.73 (s,15H); ¹³C NMR (150 MHz, CDCl₃) δ 169.1, 146.0, 145.8, 137.7, 131.0,130.7, 121.9, 115.6, 110.9, 84.8 (Cp*), 8.9 (Cp*); IR (cm⁻¹) 1564, 1455,1367, 1320, 1111, 826, 751, 512; HRMS (EI) m/z calcd. for C₁₉H₂₁ClIrNO[M]⁺: 507.0941, found: 507.0943.

Preparation Example II: Preparation of Carboxylic Acid Compound[Preparation Example 6] Preparation of 2-ethylbenzoic acid

1-bromo-2-ethylbenzene (1.38 ml, 10 mmol) was dissolved in THE (30 mL),and n-BuLi (2.5 M in hexane, 6.0 ml, 15 mmol) was slowly added theretoat −78° C. Thereafter, the mixture was stirred at the same temperaturefor 30 minutes and then anhydrous CO₂ was bubbled for 1 hour. Thetemperature of the reaction mixture was raised again, and the mixturewas stirred at room temperature for 20 minutes, quenched with asaturated aqueous NaHCO₃ solution, and washed with Et₂O. An aqueoussolution layer was acidified with a 1 N aqueous HCl solution, and thenextracted with Et₂O. The extracted solution was dried and concentratedto obtain 2-ethylbenzoic acid as a white solid (0.77 g, 50%).

[Preparation Example 7] Preparation of(S)-2-(1,3-dioxoisoindolin-2-yl)-4-methylpentanoic acid and(S)-2-(1,3-dioxoisoindolin-2-yl)-4-phenylbutanoic acid

α-Amino acid (20 mmol), phthalic anhydride (3.0 g, 20 mmol), andtriethylamine (Et₃N, 0.28 mL, 2 mmol) were added to toluene (20 mL). Thereaction mixture was heated at 130° C. for 4 hours, and moistureproduced during the reaction was collected by a water separator. Thereaction mixture was cooled to room temperature, the solvent was removedunder reduced pressure, and the reactants were dissolved in DCM (150 mL)and washed twice with an aqueous HCl solution (0.5-1.0 M, 100 mL) andthree times with a saline (100 mL). The collected organic layer wasdried with anhydrous MgSO₄, filtered with celite using DCM (30 mL), anddistilled under reduced pressure to prepare a carboxylic acid protectedby phthalimido with a yield of 95% or more.

[Preparation Example 8] Preparation of(R)-3-(1,3-dioxoisoindolin-2-yl)-4-methylpentanoic acid

A mixed solution of Boc-β-leucine (0.75 g, 3.3 mmol) and trifluoroaceticacid/dichloromethane (TFA/DCM, 10 mL, 1:1) was added to a round flaskand the solution was stirred for 1 hour. The reaction mixture wasconcentrated under reduced pressure to remove TFA, and the residue wastriturated with toluene (3 mL) and then concentrated. A β-alanine TFAsalt was dissolved in THE (15 mL), Et₃N (0.66 g, 6.5 mmol) and phthalicanhydride (0.49 g, 3.3 mmol) were added thereto, and the reactants wereheated to reflux overnight under an argon atmosphere. The reactionmixture was cooled to room temperature and concentrated under vacuum,and the residue was diluted with 1 N HCl (10 mL) and extracted withEtOAc (60 mL). The extracted organic layer was washed with a saline,dried with Na₂SO₄, and concentrated. The concentrated residue wasseparated and purified with column chromatography (DCM/MeOH, 9:1) toobtain (R)-3-(1,3-dioxoisoindolin-2-yl)-4-methylpentanoic acid as acolorless oil (0.40 g, 47%).

A carboxylic acid compound other than the carboxylic acid prepared bythe above method was purchased from Aldrich, Alfa, TCI, or the like andused without separate purification.

Preparation Example III: Preparation of Hydroxamic Acid Compound

Method A. One-Pot Synthesis of Hydroxamic Acids from Carboxylic Acids

Preparation of in-situ generated hydroxylamine: A solution ofhydroxylamine hydrochloride (1.0 g, 15 mmol) dissolved in methanol (10mL) at 0° C. was added to a solution of potassium hydroxide (0.84 g, 15mmol) dissolved in methanol (4 mL) and then the solution was stirred atthe same temperature for 15 minutes. Precipitated potassium chloride wasremoved, and then the produced filtrate was used in the next reactionwithout purification.

A carboxylilc acid compound (10 mmol) was dissolved in diethyl ether (30mL), ethylchloroformate (1.3 g, 12 mmol) and N-methylmorpholine (1.3 g,13 mmol) were added thereto at 0° C., and then the reaction mixture wasstirred for 10 minutes. After removing a solid by filtration, thefiltrate was added to a hydroxylamine (0.5 g, 15 mmol) solutiondissolved in methanol (in-situ generated hydroxylamine) and the solutionwas stirred at room temperature for 15 minutes to proceed with thereaction. The solvent was removed, and the residue was separated andpurified by column chromatography (eluent: n-hexane/EtOAc, 1:1 to 1:5)to obtain the desired hydroxamic acid compound.

Method B. One-Pot Synthesis of Hydroxamic Acids from Carboxylic Acids

A carboxylic acid compound (10 mmol) was added to dried tetrahydrofuran(THF, 30 mL), 1,1′-Carbonyldiimidazole (CDI, 15 mmol, 1.5 equiv) wasadded thereto, and the mixture was stirred for 1 hour. Hydroxylaminehydrochloride (1.39 g, 20 mmol) in a powder form was added and themixture was stirred for 16 hours. After the reaction was completed, thereaction mixture was added to a 5% aqueous KHSO₄ solution (30 mL), andextracted with EtOAc (2×30 mL). The collected organic layer was washedwith a saline (50 mL), dried with MgSO₄, concentrated, and separated andpurified by column chromatography (eluent: n-hexane/EtOAc, 1:1 to 1:5)to obtain the desired hydroxamic acid compound.

Method C. Synthesis of Hydroxamic Acids from Ester

A methyl ester compound (10.0 mmol) and hydroxylamine hydrochloride(2.08 g, 30 mmol, 3.0 equiv) were dissolved in methanol (50 mL). Solidhydroxylamine hydrochloride (3.37 g, 60 mmol, 6.0 equiv) was addedthereto and heated to reflux for 24 hours. 1 N HCl was added to thereaction mixture to adjust pH to 4 and concentrated to remove methanol.Water (50 mL) was added to the residue and extracted with EtOAc (3×50mL). The collected organic layer was dried with MgSO₄ and concentrated,and then separated and purified with column chromatography (eluent:n-hexane/EtOAc, 1:1 to 1:5) to obtain the desired hydroxamic acidcompound.

Method D. One-Pot Synthesis of Hydroxamic Acids from Carboxylic Acids

A carboxylic acid compound (2.0 mmol) was dissolved in dichloromethane(30 mL), and then oxalyl chloride (4.0 mmol) and DMF (2 drops) wereadded at 0° C. This mixture was stirred at room temperature for 2.5 to 4hours. After the solvent was removed under reduced pressure, the residuewas directly used in the next reaction without purification.

Hydroxylamine hydrochloride (1.2 equiv) and K₂CO₃ (2.0 equiv) weredissolved in a solvent in which water (8 mL) and EtOAc (16 mL) weremixed at 1:2, and then cooled to 0° C. In this solution, the acidchloride prepared above dissolved in a minimal amount of ethyl acetatewas dissolved and then the reaction mixture was stirred at roomtemperature for 12 hours. An organic layer and an aqueous solution layerwere separated, and then the aqueous solution layer was extracted withEA. The collected organic layer was dried with anhydrous MgSO₄,concentrated, and separated and purified by column chromatography(eluent: DCM/methanol=30:1 to 10:1) to obtain the desired hydroxamicacid compound.

[Preparation Example 9] Preparation of 4-phenylbutanyl hydroxamic acid

Prepared from 4-phenylbutyric acid (2 mmol scale) by Method B; Whitesolid (0.34 g, 95%); ¹H NMR (600 MHz, CDCl₃) δ 8.50 (br, 2H), 7.28-7.24(m, 2H), 7.18 (t, J=7.4 Hz, 1H), 7.14 (d, J=7.4 Hz, 2H), 2.61 (t, J=7.6Hz, 2H), 2.11 (t, J=7.6 Hz, 2H), 1.94 (p, J=7.5 Hz, 2H); ¹³C NMR (150MHz, CDCl₃) δ 171.4, 140.9, 128.4, 128.4, 126.1, 34.9, 32.1, 26.7.

[Preparation Example 10] Preparation of 4-(4-bromophenyl)butanylhydroxamic acid

Prepared from 4-(4-bromophenyl)butyric acid (2.0 mmol scale) by MethodB; solid (0.50, 96%); m.p. 99-101° C.; ¹H NMR (600 MHz, CDCl₃) δ 8.15(s, 2H), 7.40 (d, J=7.9 Hz, 2H), 7.03 (d, J=7.9 Hz, 2H), 2.59 (t, J=7.6Hz, 2H), 2.13 (t, J=7.5 Hz, 2H), 1.95 (p, J=7.5 Hz, 2H); ¹³C NMR (150MHz, CDCl₃) δ 170.8, 139.8, 131.5, 130.1, 119.9, 34.2, 31.8, 26.4; IR(cm⁻¹) 3206, 3037, 2896, 1623, 1486, 1071, 1009; HRMS (EI) m/z calcd.for C₁₀H₁₂BrNO₂ [M]⁺: 257.0051, found: 257.0049.

[Preparation Example 11] Preparation of 4-(4-fluorophenyl)butanylhydroxamic acid

Prepared from 4-(4-fluorophenyl)butyric acid (5 mmol scale) by Method B:White solid (0.71 g, 72%); m.p. 48-50° C.; ¹H NMR (600 MHz, acetone-d₆)δ 9.98 (s, 1H), 8.24 (s, 1H), 7.27-7.17 (m, 2H), 7.01 (t, J=8.8 Hz, 2H),2.60 (t, J=7.6 Hz, 2H), 2.11 (t, J=7.5 Hz, 2H), 1.88 (p, J=7.5 Hz, 2H);¹³C NMR (150 MHz, acetone-d₆) δ 170.3, 161.2 (d, J=241.4 Hz), 137.8,130.0 (d, J=8.0 Hz), 114.8 (d, J=21.1 Hz), 33.9, 31.6, 27.2; ¹⁹F NMR(564 MHz, acetone-d₆) δ −119.2 (m); IR (cm⁻¹) 3167, 2907, 1607, 1507,1222, 1068, 820; HRMS (EI) m/z calcd. for C₁₀H₁₂FNO₂ [M]⁺: 197.0852,found: 197.0850.

[Preparation Example 12] Preparation of 4-(4-nitrophenyl)butanylhydroxamic acid

Prepared from 4-(4-nitrophenyl)butyric acid (2.0 mmol scale) by MethodB: White solid (0.43 g, 95%); m.p. 109-111° C.; ¹H NMR (600 MHz,DMSO-d₆) δ 10.33 (s, 1H), 8.66 (s, 1H), 8.13 (d, J=8.7 Hz, 2H), 7.45 (d,J=8.4 Hz, 2H), 2.67 (t, J=7.8 Hz, 2H), 1.95 (t, J=7.4 Hz, 2H), 1.80 (q,J=7.6 Hz, 2H); ¹³C NMR (150 MHz, DMSO-d₆) δ 169.0, 150.6, 146.3, 130.1,123.9, 34.7, 32.0, 26.8; IR (cm⁻¹) 3187, 3037, 2902, 1628, 1510, 1346,849; HRMS (EI) m/z calcd. for C₁₀H₁₂N₂O₄ [M]⁺: 224.0797, found:224.0795.

[Preparation Example 13] Preparation of 4-(4-methoxyphenyl)butanylhydroxamic acid

Prepared from 4-(4-methoxyphenyl)butyric acid (2.0 mmol scale) by MethodB; White solid (0.41 g, 97%); m.p. 97-99° C.; ¹H NMR (600 MHz, CDCl₃) δ8.56 (br, 1H), 8.25 (s, 1H), 7.06 (d, J=8.5 Hz, 2H), 6.82 (d, J=8.7 Hz,2H), 3.78 (s, 3H), 2.57 (t, J=7.5 Hz, 2H), 2.11 (t, J=7.3 Hz, 2H), 1.94(q, J=7.6 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ 171.3, 157.9, 132.9,129.3, 113.9, 55.2, 33.9, 32.0, 26.8; IR (cm⁻¹) 3216, 3034, 2900, 1609,1509, 1241, 1028; HRMS (EI) m/z calcd. for C₁₁H₁₅NO₃ [M]⁺: 209.1052,found: 209.1052.

[Preparation Example 14] Preparation of tert-butyl[4-{4-(hydroxyamino)-4-oxobutyl}phenyl]carbamate

Prepared by Method A (2.0 mmol scale); White solid (0.44 g, 78%); m.p.120-122° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.32 (s, 1H), 9.20 (s, 1H), 8.66(s, 1H), 7.30 (d, J=8.1 Hz, 2H), 7.00 (d, J=8.5 Hz, 2H), 2.40 (t, J=7.6Hz, 2H), 1.89 (t, J=7.4 Hz, 2H), 1.69 (p, J=7.8 Hz, 2H), 1.42 (s, 9H);¹³C NMR (150 MHz, CDCl₃) δ 169.3, 153.3, 137.7, 135.6, 128.8, 118.7,79.2, 34.4, 32.2, 28.6, 27.5; IR (cm⁻¹) 3343, 3286, 1695, 1624, 1523,1239, 1162; HRMS (FAB) m/z calcd. for C₁₅H₂₂N₂O₄ [M+H]⁺: 295.1658,found: 295.1661.

[Preparation Example 15] Preparation of 2,2-dimethyl-4-phenylbutanylhydroxamic acid

Prepared from 2,2-dimethyl-4-phenylbutanoic acid by Method D; Whitesolid (0.89 g, 93%); m.p. 131-133° C.; ¹H NMR (600 MHz, CDCl₃) δ 8.42(br, 2H), 7.28-7.24 (m, 3H), 7.16 (dd, J=19.0, 7.4 Hz, 3H), 2.56-2.49(m, 2H), 1.87-1.80 (m, 2H), 1.24 (s, 6H); ¹³C NMR (150 MHz, CDCl₃) δ175.5, 141.7, 128.4, 128.3, 125.9, 42.8, 40.1, 31.2, 24.6; IR (cm⁻¹)3250, 2920, 1606, 1516, 1492, 697; HRMS (EI) m/z calcd. for C₁₂H₁₇NO₂[M]⁺: 207.1259, found: 207.1261.

[Preparation Example 16] Preparation of 2-methyl-4-phenylbutanylhydroxamic acid

Prepared from 2-methyl-4-phenylbutanoic acid by Method D: White solid(0.34 g, 88%); m.p. 126-128° C.; ¹H NMR (400 MHz, acetone-d₆) δ 10.09(s, 1H), 8.42 (s, 1H), 7.25-7.20 (m, 2H), 7.18-7.08 (m, 3H), 2.60-2.46(m, 2H), 2.31-2.19 (m, 1H), 1.96-1.83 (m, 1H), 1.72-1.53 (m, 1H), 1.08(d, J=6.9 Hz, 3H); ¹³C NMR (151 MHz, acetone-d₆, one carbon merged toothers) δ 173.4, 142.0, 128.2, 125.7, 37.0, 35.7, 33.3, 17.4; IR (cm⁻¹)3201, 3027, 2918, 1620, 1453, 1033, 697; HRMS (EI) m/z calcd. forC₁₁H₁₅NO₂ [M]⁺: 193.1103, found: 193.1103.

[Preparation Example 17] Preparation of 3-methyl-4-phenylbutanylhydroxamic acid

Prepared from 3-methyl-4-phenylbutanoic acid by Method B; White solid(1.24 g, 68%); m.p. 75-77° C.; ¹H NMR (600 MHz, CDCl₃) δ 8.53 (br, 2H),7.26 (t, J=7.2 Hz, 2H), 7.19 (t, J=7.2 Hz, 1H), 7.12 (d, J=7.2 Hz, 2H),2.59 (dd, J=13.2, 6.5 Hz, 1H), 2.47 (dd, J=13.1, 7.8 Hz, 1H), 2.30-2.23(m, 1H), 2.14 (dd, J=14.1, 4.9 Hz, 1H), 1.90-1.84 (m, 1H), 0.90 (d,J=6.4 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 170.8, 139.9, 129.1, 128.3,126.1, 43.0, 39.6, 32.4, 19.3; IR (cm⁻¹) 3208, 2920, 1632, 1453, 1030,698; HRMS (EI) m/z calcd. for C₁₁H₁₅NO₂ [M]⁺: 193.1103, found: 193.1100.

[Preparation Example 18] Preparation of2-(2,3-dihydro-1H-inden-2-yl)acetyl hydroxamic acid

Prepared from 2-indanylacetic acid by Method A: White solid (0.34 g,89%); m.p. 142-144° C.; ¹H NMR (600 MHz, DMSO-d₆) δ 10.36 (s, 1H), 8.70(s, 1H), 7.19-7.15 (m, 2H), 7.10-7.06 (m, 2H), 2.97 (dd, J=15.7, 7.8 Hz,2H), 2.71 (dt, J=14.9, 7.3 Hz, 1H), 2.55 (dd, J=15.6, 6.7 Hz, 2H), 2.08(d, J=7.5 Hz, 2H); ¹³C NMR (150 MHz, DMSO-d₆) δ 168.7, 143.0, 126.6,124.8, 38.8, 38.4, 36.6; IR (cm⁻¹) 3279, 2936, 1623, 1470, 974, 742;HRMS (EI) m/z calcd. for C₁₁H₁₃NO₂ [M]⁺: 191.0946, found: 191.0944.

[Preparation Example 19] Preparation of 2-ethylbenzyl hydroxamic acid

Prepared from 2-ethylbenzoic acid by Method D; White solid (0.29 g,86%); m.p. 114-116° C.; ¹H NMR (600 MHz, CDCl₃) δ 8.77 (br, 2H), 7.37(t, J=7.5 Hz, 1H), 7.26 (t, J=8.5 Hz, 2H), 7.16 (t, J=7.5 Hz, 1H), 2.74(q, J=7.5 Hz, 2H), 1.18 (t, J=7.5 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ168.9, 143.2, 131.4, 130.9, 129.5, 127.3, 125.8, 26.1, 15.7; IR (cm⁻¹)3186, 2969, 2873, 1617, 1517, 1018, 901; HRMS (EI) m/z calcd. forC₉H₁₁NO₂ [M]⁺: 165.0790, found: 165.0789.

[Preparation Example 20] Preparation of 2-benzylbenzyl hydroxamic acid

Prepared from 2-benzylbenzoic acid by Method D; White solid (0.41 g,39%); m.p. 146-148° C.; ¹H NMR (600 MHz, DMSO-d₆) δ 10.90 (s, 1H), 9.06(s, 1H), 7.31 (t, J=7.5 Hz, 1H), 7.26-7.20 (m, 6H), 7.15 (dd, J=12.7,7.3 Hz, 2H), 4.04 (s, 2H); ¹³C NMR (150 MHz, DMSO-d₆) δ 166.1, 140.9,139.4, 134.4, 130.1, 129.7, 128.9, 128.3, 127.5, 125.9, 125.8, 37.5; IR(cm⁻¹) 3243, 2864, 1613, 1450, 743, 701; HRMS (EI) m/z calcd. forC₁₄H₁₃NO₂ [M]: 227.0946, found: 277.0949.

[Preparation Example 21] Preparation of 4-(benzofuran-2-yl)butanylhydroxamic acid

Prepared from methyl 4-(benzofuran-2-yl)butanoate by Method C; Whitesolid (1.72 g, 78%); m.p.101-103° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.24 (s,2H), 7.47 (d, J=7.5 Hz, 1H), 7.40 (d, J=8.1 Hz, 1H), 7.20 (dt, J=20.9,7.6 Hz, 2H), 6.41 (s, 1H), 2.82 (t, J=7.0 Hz, 2H), 2.22 (t, J=7.0 Hz,2H), 2.11 (p, J=7.1 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ 193.2, 157.7,154.7, 128.6, 123.4, 122.6, 120.3, 110.8, 102.8, 31.7, 27.4, 23.3; IR(cm⁻¹) 3163, 2999, 2890, 1624, 1452, 747, 619; HRMS (EI) m/z calcd. forC₁₂H₁₃NO₃ [M]⁺: 219.0895, found: 219.0897.

[Preparation Example 22] Preparation of 4-(thiophen-2-yl)butanylhydroxamic acid

Prepared from 4-(thiophen-2-yl)butanoic acid by Method B; White solid(1.64 g, 88%); m.p. 69-71° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.76 (br, 2H),7.11 (dd, J=5.1, 1.0 Hz, 1H), 6.90 (dd, J=5.1, 3.4 Hz, 1H), 6.77 (d,J=2.6 Hz, 1H), 2.84 (t, J=7.3 Hz, 2H), 2.16 (t, J=7.3 Hz, 2H), 2.00 (p,J=7.5 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ 171.2, 143.6, 126.8, 124.7,123.4, 31.8, 28.9, 27.0; IR (cm⁻¹) 3218, 3034, 2898, 1621, 1528, 1071,704; HRMS (EI) m/z calcd. for C₈H₁₁NO₂S [M]⁺: 185.0510, found: 185.0513.

[Preparation Example 23] Preparation of 4-methylpentanyl hydroxamic acid

Prepared from 4-methylpentanoic acid by Method B; White solid (1.26 g,96%); m.p. 47-49° C.; ¹H NMR (600 MHz, CDCl₃) δ 9.18 (br, 2H), 2.14 (t,J=7.8 Hz, 2H), 1.61-1.47 (m, 3H), 0.88 (d, J=6.4 Hz, 6H); ¹³C NMR (150MHz, CDCl₃) δ 172.2, 34.2, 31.0, 27.7, 22.2; IR (cm⁻¹) 3186, 2954, 2922,1625, 1533, 1057, 586; HRMS (EI) m/z calcd. for C₆H₁₃NO₂ [M]⁺: 131.0946,found: 131.0948.

[Preparation Example 24] Preparation of 3-cyclohexylpropanyl hydroxamicacid

Prepared from 3-cyclohexylpropanoic acid by Method B; White solid (1.63g, 95%); m.p. 81-83° C.; ¹H NMR (600 MHz, CDCl₃) δ 8.78 (br, 2H), 2.15(t, J=8.3 Hz, 2H), 1.72-1.62 (m, 5H), 1.51 (q, J=7.1 Hz, 2H), 1.24-1.11(m, 4H), 0.88 (q, J=14.4, 12.6 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ172.2, 37.2, 32.9, 32.7, 30.6, 26.5, 26.2; IR (cm⁻¹) 3254, 2925, 2848,1619, 1447, 736; HRMS (EI) m/z calcd. for C₉H₁₇NO₂ [M]⁺: 171.1259,found: 171.1261.

[Preparation Example 25] Preparation of 2-isopropylbenzyl hydroxamicacid

Prepared from 2-isopropylbenzoic acid by Method D; White solid (0.32 g,88%); m.p. 89-91° C.; ¹H NMR (600 MHz, CDCl₃) δ 8.60 (br, 2H), 7.43 (t,J=7.5 Hz, 1H), 7.39 (d, J=7.8 Hz, 1H), 7.27 (d, J=4.5 Hz, 1H), 7.19 (t,J=7.4 Hz, 1H), 3.27 (p, J=6.8 Hz, 1H), 1.23 (d, J=6.8 Hz, 6H); ¹³C NMR(150 MHz, CDCl₃) δ 169.0, 147.8, 131.1, 131.0, 127.2, 126.3, 125.8,30.0, 24.1; IR (cm⁻¹) 3198, 2965, 1743, 1629, 1597, 1022, 761; HRMS (EI)m/z calcd. for C₁₀H₁₃NO₂ [M]⁺: 179.0946, found: 179.0947.

[Preparation Example 26] Preparation of Pentanyl Hydroxamic Acid

Prepared from pentanoic acid (5 mmol scale) by Method B; White solid(0.44 g, 75%); m.p. 52-54° C.; ¹H NMR (600 MHz, CDCl₃) δ 8.76 (s, 2H),2.15 (t, J=7.6 Hz, 2H), 1.61 (p, J=7.7 Hz, 2H), 1.34 (q, J=7.3 Hz, 2H),0.90 (t, J=7.3 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 171.9, 32.7, 27.4,22.2, 13.6; IR (cm⁻¹) 3204, 2930, 1626, 1457, 1039; HRMS (EI) m/z calcd.for C₅H₁₁NO₂ [M]⁺: 117.0790, found: 117.0788.

[Preparation Example 27] Preparation of 2-cyclopentylacetyl hydroxamicacid

Prepared from 2-cyclopentylacetic acid (5 mmol scale) by Method B; Whitesolid (1.33 g, 93%); m.p. 113-115° C.; ¹H NMR (600 MHz, DMSO-d₆) δ 10.28(s, 1H), 8.63 (s, 1H), 2.10 (hept, J=7.6 Hz, 1H), 1.91 (d, J=7.5 Hz,2H), 1.69-1.63 (m, 2H), 1.53 (tq, J=10.6, 6.0, 4.3 Hz, 2H), 1.47 (ddd,J=11.6, 9.7, 7.2 Hz, 2H), 1.08 (dq, J=15.6, 7.8 Hz, 2H); ¹³C NMR (150MHz, DMSO-d₆) δ 169.1, 38.8, 36.9, 32.3, 24.9; IR (cm⁻¹) 3171, 2950,2864, 1625, 1448, 981, 534; HRMS (EI) m/z calcd. for C₇H₁₃NO₂ [M]⁺:143.0946, found: 143.0945.

[Preparation Example 28] Preparation of 2-(adamantan-1-yl)acetylhydroxamic acid

Prepared from 1-adamantaneacetic acid by Method D; White solid (0.34 g,80%); m.p. 179-181° C.; ¹H NMR (600 MHz, DMSO-d₆) δ 10.21 (s, 1H), 8.60(s, 1H), 1.89 (s, 3H), 1.67 (s, 2H), 1.63 (d, J=11.9 Hz, 3H), 1.55-1.52(m, 9H); ¹³C NMR (150 MHz, DMSO-d₆) δ 167.2, 47.1, 42.5, 36.9, 32.6,28.5; IR (cm⁻¹) 3199, 2897, 2842, 1622, 1536, 1068; HRMS (EI) m/z calcd.for C₁₂H₁₉NO₂ [M]⁺: 209.1416, found: 209.1415.

[Preparation Example 29] Preparation of hex-5-enyl hydroxamic acid

Prepared from methyl hex-5-enoate(15 mmol scale) by Method C; Yellowishoil (1.54 g, 80%); ¹H NMR (400 MHz, CDCl₃) δ 9.24 (s, 2H), 5.74 (td,J=16.8, 6.7 Hz, 1H), 5.05-4.95 (m, 2H), 2.14 (t, J=7.6 Hz, 2H), 2.06 (q,J=7.2 Hz, 2H), 1.71 (p, J=7.5 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ 171.8,137.4, 115.6, 32.9, 32.1, 24.4; IR (cm⁻¹) 3197, 2903, 1628, 911; HRMS(EI) m/z calcd. for C₆H₁₁NO₂ [M]⁺: 129.0790, found: 129.0791.

[Preparation Example 30] Preparation of (E)-6-Phenylhex-5-enylhydroxamic acid

Prepared from methyl (E)-6-phenylhex-5-enoate (6.4 mmol scale) by MethodC; White solid (0.80 g, 61%); m.p. 100-102° C.; ¹H NMR (600 MHz,DMSO-d₆) δ 10.33 (s, 1H), 8.65 (s, 1H), 7.36 (d, J=7.7 Hz, 2H), 7.27 (t,J=7.5 Hz, 2H), 7.17 (t, J=7.4 Hz, 1H), 6.36 (d, J=15.9 Hz, 1H), 6.25(dt, J=15.2, 6.8 Hz, 1H), 2.13 (q, J=7.3 Hz, 2H), 1.97 (t, J=7.5 Hz,2H), 1.63 (p, J=7.5 Hz, 2H); ¹³C NMR (150 MHz, DMSO-d₆) δ 169.3, 137.7,130.5, 130.4, 128.9, 127.4, 126.3, 32.3, 32.2, 25.3; IR (cm⁻¹) 3174,3020, 2922, 1625, 964, 689; HRMS (EI) m/z calcd. for C₁₂H₁₅NO₂ [M]⁺:205.1103, found: 205.1104.

[Preparation Example 31] Preparation of 5-phenylhex-5-enyl hydroxamicacid

Prepared from methyl 5-phenylhex-5-enoate(3.5 mmol scale) by Method C;White solid(0.57 g, 79%); m.p. 77-79° C.; ¹H NMR (400 MHz, CDCl₃, twoprotons can't detected due to broadness) δ 7.37 (d, J=7.6 Hz, 2H), 7.32(t, J=6.9 Hz, 2H), 7.30-7.25 (m, 1H), 5.30 (s, 1H), 5.07 (s, 1H), 2.54(t, J=7.2 Hz, 2H), 2.14 (t, J=6.8 Hz, 2H), 1.80 (p, J=7.3 Hz, 2H); ¹³CNMR (150 MHz, CDCl₃) δ 171.0, 147.3, 140.6, 128.4, 127.6, 126.1, 113.2,34.4, 32.0, 23.5; IR (cm⁻¹) 3172, 3024, 2909, 1624, 1450, 904, 777, 707;HRMS (EI) m/z calcd. for C₁₂H₁₅NO₂ [M]⁺: 205.1103, found: 205.1100.

[Preparation Example 32] Preparation of 6-phenylhex-5-ynyl hydroxamicacid

Prepared from methyl 6-phenylhex-5-ynoate by Method C; White solid (1.9g, 93%); m.p. 66-68° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.66 (s, 2H),7.39-7.34 (m, 2H), 7.28-7.23 (m, 3H), 2.45 (t, J=6.8 Hz, 2H), 2.32 (t,J=7.4 Hz, 2H), 1.92 (p, J=7.2 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ 171.1,131.5, 128.2, 127.8, 123.5, 88.4, 81.8, 31.6, 24.2, 18.7; IR (cm⁻¹)3269, 3200, 2903, 1624, 1438, 1035, 752, 689; HRMS (EI) m/z calcd. forC₁₂H₁₃NO₂ [M]⁺: 203.0946, found: 203.0945.

[Preparation Example 33] Preparation of 7-phenylhept-5-ynyl hydroxamicacid

Prepared from methyl 7-phenylhept-5-ynoic acid (2 mmol scale) by MethodB; Yellow resin (0.33 g, 75%); ¹H NMR (600 MHz, acetone-d₆) δ 10.36 (s,1H), 9.29 (s, 1H), 7.35-7.33 (m, 2H), 7.29 (t, J=7.6 Hz, 2H), 7.20 (t,J=7.3 Hz, 1H), 3.56 (s, 2H), 2.32-2.22 (m, 4H), 1.82 (p, J=7.3 Hz, 2H);¹³C NMR (150 MHz, acetone-d₆) δ 170.5, 137.6, 128.4, 127.8, 126.3, 81.4,78.4, 31.5, 25.0, 24.5, 18.0; IR (cm⁻¹) 3196, 2934, 1638, 1451, 1264,766, 694; HRMS (ESI) m/z calcd. for C₁₃H₁₅NO₂ [M+H]⁺: 218.1176, found:218.1157.

[Preparation Example 34] Preparation of hept-5-ynyl hydroxamic acid

Prepared from hept-5-ynoic acid by Method B; White solid (1.45 g, 62%);m.p. 74-76° C.; ¹H NMR (600 MHz, acetone-d₆) δ 10.07 (s, 1H), 8.78 (s,1H), 2.19 (t, J=7.3 Hz, 2H), 2.14-2.10 (m, 2H), 1.76-1.66 (m, 5H); ¹³CNMR (150 MHz, acetone-d₆) δ 169.8, 77.9, 75.7, 31.2, 24.9, 17.8, 2.3; IR(cm⁻¹) 3255, 3060, 2740, 1657, 1433, 1021, 444; HRMS (EI) m/z calcd. forC₇H₁₁NO₂ [M]⁺: 141.0790, found: 141.0790.

[Preparation Example 35] Preparation of 3-benzylpentanyl hydroxamic acid

Prepared from 3-benzylpentanoic acid (1.5 mmol scale) by Method D; Whitesolid (0.28 g, 89%); m.p. 90-92° C.; ¹H NMR (400 MHz, CDCl₃, two protonscan't detected due to broadness) δ 7.29 (t, J=7.3 Hz, 2H), 7.20 (t,J=7.3 Hz, 1H), 7.15 (d, J=7.5 Hz, 2H), 2.68 (dd J=13.6, 6.6 Hz, 1H),2.51 (dd, J=13.6, 7.3 Hz, 1H), 2.25-2.09 (m, 1H), 2.04 (d, J=6.7 Hz,2H), 1.37 (p, J=7.4 Hz, 2H), 0.92 (t, J=7.3 Hz, 3H); ¹³C NMR (150 MHz,CDCl₃) δ 171.2, 140.0, 129.2, 128.3, 126.1, 39.6, 38.5, 36.6, 25.9,10.9; IR (cm⁻¹) 3223, 2961, 2928, 1636, 1494, 1453, 699; HRMS (FAB) m/zcalcd. for C₁₂H₁₇NO₂ [M+H]208.1338, found: 208.1338.

[Preparation Example 36] Preparation of 3-benzyl-4-methylpentanylhydroxamic acid

Prepared from 3-benzyl-4-methylpentanoic acid (1.8 mmol scale) by MethodD; Yellow solid (0.34 g, 82%); m.p. 80-82° C.; ¹H NMR (400 MHz, CD₂Cl₂)8.97 (s, 2H), 7.29 (t, J=7.2 Hz, 2H), 7.24-7.14 (m, 3H), 2.64 (dd,J=13.1, 6.0 Hz, 1H), 2.45 (dd, J=12.4, 6.8 Hz, 1H), 2.19-2.02 (m, 2H),1.98-1.86 (m, 1H), 1.78-1.65 (m, 1H), 0.89 (dd, J=14.3, 6.5 Hz, 6H); ¹³CNMR (100 MHz, CD₂Cl₂) δ 172.0, 141.1, 129.4, 128.5, 126.1, 43.1, 36.8,33.7, 28.6, 18.9, 18.3; IR (cm⁻¹) 3205, 2956, 1635, 698; HRMS (FAB) m/zcalcd. for C₁₃H₁₉NO₂ [M+H]⁺: 222.1494, found: 222.1496.

[Preparation Example 37] Preparation of(S)-2-(1,3-dioxoisoindolin-2-yl)-4-methylpentanylhydroxamic acid

Prepared from (S)-2-(1,3-dioxoisoindolin-2-yl)-4-methylpentanoic acid byMethod D; White solid (0.45 g, 81%); m.p. 155-157° C.; ¹H NMR (600 MHz,CDCl₃, one proton can't detected due to broadness) δ 9.33 (s, 1H), 7.87(dd, J=5.5, 3.1 Hz, 2H), 7.76 (dd, J=5.5, 3.0 Hz, 2H), 5.01 (dd, J=11.2,5.2 Hz, 1H), 2.34-2.20 (m, 1H), 1.83 (ddd, J=14.2, 9.4, 5.3 Hz, 1H),1.46 (q, J=7.8, 7.0 Hz, 1H), 0.93 (dd, J=6.7, 2.3 Hz, 6H); ¹³C NMR (150MHz, CDCl₃) δ 168.1, 167.8, 134.5, 131.4, 123.7, 51.4, 37.5, 25.0, 22.9,21.3; IR (cm⁻¹) 3228, 2957, 1715, 1644, 1380, 717; HRMS (EI) m/z calcd.for C₁₄H₁₆N₂O₄ [M]⁺: 276.1110, found: 276.1111.

[Preparation Example 38] Preparation of(S)-2-(1,3-dioxoisoindolin-2-yl)-4-phenylbutanylhydroxamic acid

Prepared from (S)-2-(1,3-dioxoisoindolin-2-yl)-4-phenylbutanoic acid(3.0 mmol scale) by Method D; White solid (0.49 g, 76%); m.p. 114-116°C.; ¹H NMR (600 MHz, DMSO-d₆) δ 10.80 (s, 1H), 8.87 (s, 1H), 7.88-7.83(m, 4H), 7.18 (t, J=7.5 Hz, 2H), 7.11 (d, J=7.5 Hz, 2H), 7.07 (t, J=7.4Hz, 1H), 4.62 (dd, J=10.4, 4.8 Hz, 1H), 2.58-2.51 (m, 2H), 2.48-2.41 (m,2H); ¹³C NMR (150 MHz, DMSO-d₆) δ 167.7, 165.2, 140.6, 134.4, 131.7,128.3, 128.3, 125.8, 123.1, 51.4, 32.1, 29.3; IR (cm⁻¹) 3303, 3165,2954, 1695, 1653, 1386, 712; HRMS (EI) m/z calcd. for C₁₈H₁₆N₂O₄ [M]⁺:324.1110, found: 324.1112.

[Preparation Example 39] Preparation of(R)-3-(1,3-dioxoisoindolin-2-yl)-4-methylpentanyl hydroxamic acid

Prepared from (R)-3-(1,3-dioxoisoindolin-2-yl)-4-methylpentanoicacid(2.0 mmol scale) by Method B; White solid (0.39 g, 71%); m.p.154-156° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.44 (s, 1H), 8.66 (s, 1H),7.86-7.79 (m, 4H), 4.17 (td, J=9.8, 4.8 Hz, 1H), 2.75 (dd, J=14.7, 10.2Hz, 1H), 2.56 (dd, J=14.7, 4.7 Hz, 1H), 2.24-2.09 (m, 1H), 0.97 (d,J=6.7 Hz, 3H), 0.77 (d, J=6.7 Hz, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ168.4, 167.2, 134.9, 131.6, 123.5, 54.5, 33.2, 31.0, 20.4, 20.0; IR(cm⁻¹) 3255, 2963, 2872, 1695, 1359, 719; HRMS (EI) m/z calcd. forC₁₄H₁₆N₂O₄ [M]⁺: 276.1110, found: 276.1113.

[Preparation Example 40] Preparation of2-(1-((1,3-dioxoisoindolin-2-yl)methyl)cyclohexyl)acetylhydroxamic acid

Prepared from 2-(1-((1,3-dioxoisoindolin-2-yl)methyl)cyclohexyl)aceticacid (2.0 mmol scale) by Method D: White solid (0.43 g, 68%); m.p.152-154° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.40 (s, 1H), 8.77 (s, 1H),7.85 (m, 4H), 3.65 (s, 2H), 2.06 (s, 2H), 1.61-1.06 (m, 10H); ¹³C NMR(100 MHz, DMSO-d₆) δ 169.5, 167.8, 135.0, 132.4, 123.7, 46.8, 38.9,38.8, 33.2, 25.9, 21.8; IR (cm⁻¹) 3274, 3140, 2922, 2868, 1697, 1396,713; HRMS (EI) m/z calcd. for C₁₇H₂₀N₂O₄[M]⁺: 316.1423, found: 316.1422.

[Preparation Example 41] Preparation of tert-butyl([1-{2-(hydroxyamino)-2-oxoethyl}cyclohexyl]methyl)carbamate

Prepared from 2-(1-[{(tert-butoxycarbonyl)amino}methyl]cyclohexyl)aceticacid(2.0 mmol scale) by Method B; White solid (0.39 g, 68%); m.p.129-131° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.40 (s, 1H), 8.75 (s, 1H),6.65 (s, 1H), 2.94 (d, J=6.3 Hz, 2H), 1.88 (s, 2H), 1.40-1.14 (m, 19H);¹³C NMR (100 MHz, DMSO-d₆) δ 167.8, 156.5, 78.0, 47.3, 40.5, 37.2, 33.3,28.7, 26.1, 21.5; IR (cm⁻¹) 3244, 2926, 1683, 1651, 1508, 1453, 1365,1250, 1166; HRMS (FAB) m/z calcd. for C₁₄H₂₆N₂O₄ [M+H]⁺: 287.1971,found: 287.1968.

[Preparation Example 42] Preparation ofanti-(Z)-2-(3-oxo-2-(pent-2-en-1-yl)cyclopentyl)acetyl hydroxamic acid

Prepared from Jasmonic acid by Method D; White solid (0.35 g, 78%); m.p.91-93° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.40 (s, 1H), 8.72 (s, 1H), 5.34(q, J=7.8 Hz, 1H), 5.23-5.14 (m, 1H), 2.27-2.11 (m, 5H), 2.04-1.86 (m,6H), 1.43-1.30 (m, 1H), 0.87 (t, J=7.5 Hz, 3H); ¹³C NMR (150 MHz,DMSO-d₆) δ 219.2, 168.1, 133.3, 126.1, 53.8, 38.0, 37.7, 37.4, 26.9,25.3, 20.5, 14.5; IR (cm⁻¹) 3206, 2931, 1733, 1647, 733, 701; HRMS (EI)m/z calcd. for C₁₂H₁₉NO₃ [M]⁺: 225.1365, found: 225.1366.

[Preparation Example 43] Preparation of(4R)-4-((3R,8R,9S,10S,13R,14S,17R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoylhydroxamic acid

Prepared from 3α-methyl lithocholic acid (5.0 mmol scale) by Method B;White solid (1.38 g, 68%); m.p.160-162° C.; ¹H NMR (600 MHz, DMSO-d₆) δ10.31 (s, 1H), 8.63 (s, 1H), 3.21 (s, 3H), 3.10 (tt, J=10.2, 4.3 Hz,1H), 1.99-1.90 (m, 2H), 1.83 (dq, J=31.7, 12.8, 10.5 Hz, 3H), 1.76-1.62(m, 3H), 1.55 (dd, J=23.8, 11.6 Hz, 3H), 1.33 (t, J=10.3 Hz, 6H),1.23-1.11 (m, 5H), 1.10-0.99 (m, 5H), 0.92-0.86 (m, 7H), 0.61 (s, 3H);¹³C NMR (150 MHz, DMSO-d₆, one carbon merged to solvent peak) δ 169.9,79.9, 56.4, 56.0, 55.2, 42.7, 41.8, 40.1, 35.8, 35.3, 35.3, 34.9, 32.8,31.9, 29.6, 28.2, 27.3, 26.9, 26.5, 24.3, 23.7, 20.6, 18.7, 12.3; IR(cm⁻¹) 3224, 2925, 2861, 1650, 1446, 1372, 1091; HRMS (ESI) m/z calcd.for C₂₅H₄₃NO₃ [M+H]⁺: 406.3316, found: 406.3286.

[Preparation Example 44] Preparation of3,7-dimethyloct-6-enoylhydroxamic acid

Prepared from citronellic acid (5.0 mmol scale) by Method B; White solid(0.62 g, 67%); m.p. 49-51° C.; ¹H NMR (600 MHz, CDCl₃) δ 9.13 (br, 1H),8.63 (s, 1H), 5.05 (t, J=7.3 Hz, 1H), 2.15 (dd, J=13.6, 5.4 Hz, 1H),2.03-1.91 (m, 3H), 1.88 (dd, J=13.6, 8.6 Hz, 1H), 1.66 (s, 3H), 1.57 (s,3H), 1.34 (td, J=14.9, 14.3, 6.0 Hz, 1H), 1.19 (dt, J=13.3, 6.7 Hz, 1H),0.91 (d, J=6.5 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 171.2, 131.7, 124.1,40.5, 36.7, 30.2, 25.7, 25.4, 19.3, 17.6; IR (cm⁻¹) 3191, 2963, 2913,1632, 1451, 735; HRMS (EI) m/z calcd. for C₁₀H₁₉NO₂ [M]⁺: 185.1416,found: 185.1417.

[Preparation Example 45] Preparation of(S)-2-((2R,4aS)-4a,8-dimethyl-7-oxo-1,2,3,4,4a,7-hexahydronaphthalen-2-yl)propanoylhydroxamic acid

Prepared from(S)-2-((2R,4aS)-4a,8-dimethyl-7-oxo-1,2,3,4,4a,7-hexahydronaphthalen-2-yl)propanoicacid (1.0 mmol scale) by Method B; White solid (0.15 g, 58%); m.p.119-121° C.; ¹H NMR (400 MHz, acetone-d₆, two protons can't detected dueto broadness) δ 6.83 (d, J=9.8 Hz, 1H), 6.07 (d, J=9.8 Hz, 1H),2.84-2.74 (m, 1H), 2.26-2.14 (m, 1H), 1.94-1.85 (m, 1H), 1.83-1.71 (m,4H), 1.60-1.41 (m, 2H), 1.32-1.19 (m, 1H), 1.19 (s, 3H), 1.14-1.09 (m,4H); ¹³C NMR (100 MHz, acetone-d₆) δ 185.2, 172.6, 159.4, 156.6, 128.7,125.9, 43.0, 42.6, 40.3, 37.9, 31.8, 24.7, 22.9, 15.0, 9.8; IR (cm⁻¹)3186, 2921, 1650, 1596, 1451, 949, 834; HRMS (EI) m/z calcd. forC₁₅H₂₁NO₃ [M]⁺: 263.1521, found: 263.1519.

Preparation Example IV: Preparation of3-substituted-1,4,2-dioxazol-5-one compound

A hydroxamic acid compound (5.0 mmol) was dissolved in dichloromethane(50 mL), 1,1′-carbonyldiimidazole (0.81 g, 5.0 mmol) was added theretoall together at room temperature, and the mixture was stirred for 30minutes. After the reaction was completed, the product was quenched with1 N HCl (30 mL), extracted with dichloromethane (50 mL×3), and driedwith magnesium sulfate, and the solvent was removed under reducedpressure. The residue was filtered with silica and washed withdichloromethane (10 ml×2), and then the filtrate was distilled underreduced pressure to obtain the title compound.

The following compound was prepared in the same manner as in the above,except that the starting material was different.

[Preparation Example 46] Preparation of3-(3-phenylpropyl)-1,4,2-dioxazol-5-one

Colorless liquid (0.82 g, 80%); ¹H NMR (600 MHz, CDCl₃) δ 7.32 (t, J=7.5Hz, 2H), 7.23 (t, J=7.3 Hz, 1H), 7.18 (d, J=7.5 Hz, 2H), 2.75 (t, J=7.4Hz, 2H), 2.62 (t, J=7.5 Hz, 2H), 2.07 (p, J=7.4 Hz, 2H); ¹³C NMR (150MHz, CDCl₃) δ 166.4, 154.0, 139.7, 128.6, 128.4, 126.5, 34.5, 25.9,24.0; IR (cm⁻¹) 3207, 2913, 1827, 1634, 1452, 980; HRMS (EI) m/z calcd.for C₁₁H₁₁NO₃ [M]⁺: 205.0739, found: 205.0737.

[Preparation Example 47] Preparation of3-(3-(4-bromophenyl)propyl)-1,4,2-dioxazol-5-one

White solid (1.3 g, 93%); ¹H NMR (400 MHz, CDCl₃) δ 7.44 (d, J=8.2 Hz,2H), 7.06 (d, J=8.2 Hz, 2H), 2.70 (t, J=7.5 Hz, 2H), 2.62 (t, J=7.4 Hz,2H), 2.04 (p, J=7.4 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ 166.2, 154.0,138.7, 131.8, 130.1, 120.4, 33.9, 25.7, 23.9; IR (cm 1) 2925, 1867,1826, 1631, 1152, 985; HRMS (EI) m/z calcd. for C₁₁H₁₀BrNO₃ [M]⁺:282.9844, found: 282.9843.

[Preparation Example 48] Preparation of3-(3-(4-fluorophenyl)propyl)-1,4,2-dioxazol-5-one

Colorless liquid (0.41 g, 90%); ¹H NMR (600 MHz, CD₂Cl₂) δ 7.22-7.12 (m,2H), 7.07-6.95 (m, 2H), 2.72 (t, J=7.5 Hz, 2H), 2.63 (t, J=7.5 Hz, 2H),2.03 (p, J=7.5 Hz, 2H); ¹³C NMR (150 MHz, CD₂Cl₂) δ 166.6, 161.5 (d,J=243.4 Hz), 154.1, 135.9 (d, J=3.1 Hz), 129.9 (d, J=7.8 Hz), 115.2 (d,J=21.3 Hz), 33.7, 26.0, 24.0; ¹⁹F NMR (564 MHz, CD₂Cl₂) δ −117.7(m); IR(cm⁻¹) 2934, 1870, 1825, 1508, 1218, 1150, 981; HRMS (EI) m/z calcd. forC₁₁H₁₀FNO₃ [M]⁺: 223.0645, found: 223.0646.

[Preparation Example 49] Preparation of3-(3-(4-nitrophenyl)propyl)-1,4,2-dioxazol-5-one

White solid (1.0 g, 81%); ¹H NMR (600 MHz, CDCl₃) δ 8.18 (d, J=8.6 Hz,2H), 7.36 (d, J=8.6 Hz, 2H), 2.86 (t, J=7.7 Hz, 2H), 2.67 (t, J=7.4 Hz,2H), 2.12 (p, J=7.5 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) 165.9, 153.8,147.5, 146.9, 129.2, 124.0, 34.4, 25.4, 24.1; IR (cm⁻¹) 1828, 1536,1346, 1152, 990, 948; HRMS (EI) m/z calcd. for C₁₁H₁₀N₂O₅ [M]⁺:250.0590,found: 250.0592.

[Preparation Example 50] Preparation of3-(3-(4-methoxyphenyl)propyl)-1,4,2-dioxazol-5-one

Yellowish oil (1.1 g, 95%); ¹H NMR (600 MHz, CDCl₃) δ 7.09 (d, J=8.3 Hz,2H), 6.85 (d, J=8.3 Hz, 2H), 3.80 (s, 3H), 2.69 (t, J=7.4 Hz, 2H), 2.60(t, J=7.4 Hz, 2H), 2.03 (p, J=7.4 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ166.5, 158.3, 154.1, 131.7, 129.4, 114.1, 55.3, 33.6, 26.1, 23.9; IR(cm⁻¹) 2936, 1870, 1825, 1510, 1242, 981; HRMS (EI) m/z calcd. forC₁₂H₁₃NO₄ [M]⁺: 235.0845, found: 235.0846.

[Preparation Example 51] Preparation of tert-butyl[4-{3-(5-oxo-1,4,2-dioxazol-3-yl)propyl}phenyl]carbamate

Prepared on a 1.2 mmol scale. Due to the stability of a Boc group, thedesired compound was obtained through a silica filter directly usingdichloromethane without quenching with 1 N HCl after the reaction. Whitesolid (0.30 g, 78%); ¹H NMR (600 MHz, CDCl₃) δ 7.28 (d, J=7.9 Hz, 2H),7.07 (d, J=8.5 Hz, 2H), 6.43 (s, 1H), 2.66 (t, J 7.3 Hz, 2H), 2.58 (t,J=7.5 Hz, 2H), 2.00 (p, J=7.5 Hz, 2H), 1.49 (s, 9H); ¹³C NMR (150 MHz,CDCl₃) δ 166.4, 154.1, 152.8, 136.8, 134.4, 128.9, 118.9, 80.5, 33.8,28.3, 25.9, 23.9; IR (cm⁻¹) 3334, 2978, 1870, 1825, 1703, 1520, 1151;HRMS (FAB) m/z calcd. for C₁₆H₂₀N₂O₅[M+H]⁺: 321.1450, found: 321.1448.

[Preparation Example 52] Preparation of3-(2-Methyl-4-phenylbutan-2-yl)-1,4,2-dioxazol-5-one

Colorless liquid (0.92 g, 79%); ¹H NMR (600 MHz, CDCl₃) δ 7.29 (t, J=7.5Hz, 2H), 7.21 (t, J=7.4 Hz, 1H), 7.16 (d, J=7.6 Hz, 2H), 2.64-2.59 (m,2H), 1.98-1.93 (m, 2H), 1.40 (s, 6H); ¹³C NMR (150 MHz, CDCl₃) δ 171.3,154.3, 140.4, 128.5, 128.3, 126.3, 41.2, 35.9, 30.8, 24.2; IR (cm⁻¹)2978, 1869, 1824, 1110, 974; HRMS (EI) m/z calcd. for C₁₃H₁₅NO₃ [M]⁺:233.1052, found: 233.1051.

[Preparation Example 53] Preparation of3-(4-phenylbutan-2-yl)-1,4,2-dioxazol-5-one

Colorless liquid (0.42 g, 95%); ¹H NMR (600 MHz, CD₂Cl₂) δ 7.30 (t,J=7.4 Hz, 2H), 7.24-7.16 (m, 3H), 2.91-2.81 (m, 1H), 2.76-2.64 (m, 2H),2.14-2.03 (m, 1H), 1.97-1.86 (m, 1H), 1.35 (d, J=7.0 Hz, 3H); ¹³C NMR(150 MHz, CD₂Cl₂) δ 169.6, 154.2, 140.4, 128.5, 128.3, 126.2, 34.0,32.6, 30.6, 16.0; IR (cm⁻¹) 3332, 1870, 1826, 1264, 976, 734; HRMS (EI)m/z calcd. for C₁₂H₁₃NO₃ [M]⁺: 219.0895, found: 219.0893.

[Preparation Example 54] Preparation of3-(2-methyl-3-phenylpropyl)-1,4,2-dioxazol-5-one

Prepared on a 3.0 mmol scale. Yellowish oil (0.61 g, 95%); ¹H NMR (600MHz, CDCl₃) δ 7.31 (t, J=7.3 Hz, 2H), 7.24 (t, J=7.3 Hz, 1H), 7.16 (d,J=7.2 Hz, 2H), 2.70-2.59 (m, 3H), 2.44 (dd, J=15.4, 8.0 Hz, 1H), 2.30(dq, J=14.0, 6.9 Hz, 1H), 1.05 (d, J=6.6 Hz, 3H); ¹³C NMR (150 MHz,CDCl₃) δ 165.9, 154.0, 138.8, 129.1, 128.6, 126.6, 42.7, 32.1, 31.0,19.6; IR (cm⁻¹) 2929, 1875, 1826, 1631, 1145, 980; HRMS (EI) m/z calcd.for C₁₂H₁₃NO₃ [M]⁺: 219.0895, found: 219.0894.

[Preparation Example 55] Preparation of3-((2,3-dihydro-1H-inden-2-yl)methyl)-1,4,2-dioxazol-5-one

Colorless oil (0.43 g, 40%); ¹H NMR (600 MHz, CDCl₃) δ 7.24-7.19 (m,2H), 7.19-7.14 (m, 2H), 3.21 (dd, J=15.6, 7.8 Hz, 2H), 2.91 (hept,J=7.8, 7.2 Hz, 1H), 2.78 (d, J=7.4 Hz, 2H), 2.75 (dd, J=15.6, 6.4 Hz,2H); ¹³C NMR (150 MHz, CDCl₃) δ 165.9, 154.0, 141.3, 126.8, 124.6, 38.7,35.5, 30.3; IR (cm⁻¹) 1878, 1820, 1353, 1143, 990, 744; HRMS (EI) m/zcalcd. for C₁₂H₁₁NO₃ [M]⁺: 217.0739, found: 217.0740.

[Preparation Example 56] Preparation of3-(2-ethylphenyl)-1,4,2-dioxazol-5-one

Prepared at 3.0 mmol scale. Colorless oil (0.28 g, 48%); ¹H NMR (600MHz, CDCl₃) δ 7.75 (d, J=7.8 Hz, 1H), 7.56 (t, J=7.7 Hz, 1H), 7.41 (d,J=7.8 Hz, 1H), 7.37 (t, J=7.7 Hz, 1H), 2.97 (q, J=7.5 Hz, 2H), 1.27 (t,J=7.5 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 163.9, 153.7, 145.3, 133.4,130.4, 129.1, 126.5, 118.6, 27.6, 14.9; IR (cm⁻¹) 1857, 1827, 1608,1339, 1055, 969, 753; HRMS (EI) m/z calcd. for C₁₀H₉NO₃ [M]⁺: 191.0582,found: 191.0581.

[Preparation Example 57] Preparation of3-(2-benzylphenyl)-1,4,2-dioxazol-5-one

White solid (0.77 g, 61%); ¹H NMR (600 MHz, CDCl₃) δ 7.79 (d, J=7.9 Hz,1H), 7.55 (t, J=7.6 Hz, 1H), 7.41 (t, J=7.6 Hz, 1H), 7.32-7.28 (m, 3H),7.23 (t, J=7.4 Hz, 1H), 7.13 (d, J=7.6 Hz, 2H), 4.34 (s, 2H); ¹³C NMR(150 MHz, CDCl₃) δ 163.7, 153.5, 141.7, 138.8, 133.3, 131.9, 129.3,129.0, 128.6, 127.0, 126.5, 119.3, 39.9; IR (cm⁻¹) 1861, 1829, 1348,1173, 1042, 978; HRMS (EI) m/z calcd. for C₁₅H₁₁NO₃ [M]⁺: 253.0739,found: 253.0739.

[Preparation Example 58] Preparation of3-(3-(benzofuran-2-yl)propyl)-1,4,2-dioxazol-5-one

Colorless oil (1.21 g, 99%); ¹H NMR (400 MHz, CDCl₃) δ 7.54-7.49 (m,1H), 7.43 (d, J=8.2 Hz, 1H), 7.28-7.18 (m, 2H), 6.47 (s, 1H), 2.93 (t,J=7.1 Hz, 2H), 2.72 (t, J=7.5 Hz, 2H), 2.20 (p, J=7.3 Hz, 2H); ¹³C NMR(150 MHz, CDCl₃) δ 166.1, 156.3, 154.8, 154.0, 128.5, 123.7, 122.7,120.5, 110.9, 103.4, 27.2, 24.0, 22.6; IR (cm⁻¹) 1880, 1860, 1830, 1151,981, 751; HRMS (EI) m/z calcd. for C₁₃H₁₁NO₄ [M]⁺: 245.0688, found:245.0690.

[Preparation Example 59] Preparation of3-(3-(thiophen-2-yl)propyl)-1,4,2-dioxazol-5-one

Colorless liquid (0.99 g, 94%); ¹H NMR (600 MHz, CDCl₃) δ 7.17 (dd,J=5.1, 1.2 Hz, 1H), 6.94 (dd, J=5.2, 3.4 Hz, 1H), 6.85-6.81 (m, 1H),2.98 (t, J=7.2 Hz, 2H), 2.67 (t, J=7.5 Hz, 2H), 2.11 (p, J=7.3 Hz, 2H);¹³C NMR (150 MHz, CDCl₃) δ 166.2, 154.0, 142.2, 127.0, 125.2, 123.9,28.6, 26.2, 23.8; IR (cm⁻¹) 1868, 1823, 1635, 1148, 980, 695; HRMS (EI)m/z calcd. for C₉H₉NO₃S [M]: 211.0303, found: 211.0301.

[Preparation Example 60] Preparation of 3-isopentyl-1,4,2-dioxazol-5-one

Colorless oil (0.67 g, 85%); ¹H NMR (600 MHz, CDCl₃) δ 2.61 (t, J=7.6Hz, 2H), 1.68-1.57 (m, 3H), 0.94 (d, J=6.4 Hz, 6H); ¹³C NMR (150 MHz,CDCl₃) δ 166.9, 154.2, 33.1, 27.4, 22.8, 21.9; IR (cm⁻¹) 2960, 1865,1825, 1147, 981, 761; HRMS (EI) m/z calcd. for C₇H₁₁NO₃ [M]⁺: 157.0739,found: 157.0738.

[Preparation Example 61] Preparation of3-(2-cyclohexylethyl)-1,4,2-dioxazol-5-one

Colorless oil (0.95 g, 96%); ¹H NMR (600 MHz, CDCl₃) δ 2.63 (t, J=8.0Hz, 2H), 1.73 (d, J=10.9 Hz, 4H), 1.67 (d, J=12.6 Hz, 1H), 1.61 (q,J=7.3 Hz, 2H), 1.35-1.12 (m, 4H), 0.93 (q, J=12.0 Hz, 2H); ¹³C NMR (150MHz, CDCl₃) δ 167.0, 154.2, 36.8, 32.7, 31.7, 26.3, 26.0, 22.3; IR(cm⁻¹) 2922, 2851, 1867, 1825, 1145, 974, 762; HRMS (EI) m/z calcd. forC₁₀H₁₅NO₃ [M]⁺: 197.1052, found: 197.1050.

[Preparation Example 62] Preparation of3-(2-isopropylphenyl)-1,4,2-dioxazol-5-one

Prepared on a 0.84 mmol scale; Colorless oil (0.12 g, 67%); ¹H NMR (600MHz, CDCl₃) δ 7.69 (d, J=8.0 Hz, 1H), 7.59 (t, J=7.6 Hz, 1H), 7.53 (d,J=8.0 Hz, 1H), 7.35 (t, J=7.6 Hz, 1H), 3.60 (hept, J=6.8 Hz, 1H), 1.29(d, J=6.8 Hz, 6H); ¹³C NMR (150 MHz, CDCl₃) δ 164.1, 153.8, 150.0,133.5, 129.3, 126.9, 126.4, 118.3, 30.3, 23.6; IR (cm⁻¹) 2967, 1858,1829, 1337, 1047, 970, 758; HRMS (EI) m/z calcd. for C₁₁H₁₁NO₃ [M]⁺:205.0739, found: 205.0737.

[Preparation Example 63] Preparation of(S)-3-(3-Methylpentyl)-1,4,2-dioxazol-5-one

Prepared on a 7.65 mmol scale; colorless liquid (0.93 g, 71%, 2 stepsyield from carboxylic acid); ¹H NMR (400 MHz, CDCl₃) δ 2.73-2.56 (m,2H), 1.82-1.71 (m, 1H), 1.60-1.49 (m, 1H), 1.49-1.35 (m, 2H), 1.29-1.18(m, 1H), 0.97-0.88 (m, 6H); ¹³C NMR (100 MHz, CDCl₃) δ 167.2, 154.4,33.9, 31.2, 29.1, 22.8, 18.7, 11.3; IR (cm⁻¹) 2962, 1859, 1825, 1147,979; HRMS (ESI) m/z calcd. for C₈H₁₃NO₃ [M+Na]⁺: 194.0788, found:190.0794.

[Preparation Example 64] Preparation of 3-butyl-1,4,2-dioxazol-5-one

Prepared on a 3.5 mmol scale; Colorless liquid (0.39 g, 78%); ¹H NMR(600 MHz, CDCl₃) δ 2.63 (t, J=7.5 Hz, 2H), 1.71 (p, J=7.6 Hz, 2H), 1.44(h, J=7.4 Hz, 2H), 0.97 (t, J=7.4 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ166.7, 154.2, 26.5, 24.4, 21.8, 13.4; IR (cm⁻¹) 2963, 1824, 1634, 1148,980, 761; HRMS (EI) m/z calcd. for C₆H₉NO₃ [M]⁺: 143.0582, found:143.0583.

[Preparation Example 65] Preparation of3-(cyclopentylmethyl)-1,4,2-dioxazol-5-one

Prepared on a 4.4 mmol scale; Colorless liquid (0.70 g, 94%); ¹H NMR(600 MHz, CDCl₃) δ 2.60 (d, J=7.4 Hz, 2H), 2.23 (hept, J=7.8 Hz, 1H),1.88 (dq, J=11.9, 6.8 Hz, 2H), 1.71-1.64 (m, 2H), 1.64-1.56 (m, 2H),1.24 (dq, J=15.0, 7.6 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ 166.4, 154.2,35.9, 32.3, 30.5, 24.9; IR (cm⁻¹) 2952, 2869, 1868, 1825, 1631, 1149,980; HRMS (EI) m/z calcd. for C₈H₁₁NO₃ [M]⁺: 169.0739, found: 169.0739.

[Preparation Example 66] Preparation of3-((adamantan-1-yl)methyl)-1,4,2-dioxazol-5-one

White solid (1.13 g, 96%); ¹H NMR (600 MHz, CDCl₃) δ 2.36 (s, 2H), 2.01(s, 3H), 1.72 (d, J=12.2 Hz, 3H), 1.65-1.58 (m, 9H); ¹³C NMR (150 MHz,CDCl₃) δ 165.0, 154.3, 42.1, 38.8, 36.3, 33.2, 28.3; IR (cm⁻¹) 2903,2885, 2848, 1813, 1152, 985; HRMS (EI) m/z calcd. for C₁₃H₁₇NO₃ [M]⁺:235.1208, found: 235.1206.

[Preparation Example 67] Preparation of 3-neopentyl-1,4,2-dioxazol-5-one

Colorless oil (0.55 g, 70%); ¹H NMR (600 MHz, CDCl₃) δ 2.51 (s, 2H),1.08 (s, 9H); ¹³C NMR (150 MHz, CDCl₃) δ 165.6, 154.2, 38.4, 31.3, 29.4;IR (cm⁻¹) 2963, 1829, 1629, 1352, 1143, 981.

[Preparation Example 68] Preparation of3-(pent-4-en-1-yl)-1,4,2-dioxazol-5-one

Colorless oil (0.44 g, 60%); ¹H NMR (600 MHz, CDCl₃) δ 5.76 (ddt,J=17.0, 10.4, 6.7 Hz, 1H), 5.12-5.04 (m, 2H), 2.64 (t, J=7.5 Hz, 2H),2.18 (q, J=6.6 Hz, 2H), 1.84 (p, J=7.4 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃)δ 166.5, 154.1, 136.2, 116.6, 32.4, 23.9, 23.5; IR (cm⁻¹) 1868, 1824,1638, 1148, 979, 761; HRMS (EI) m/z calcd. for C₇H₉NO₃ [M]⁺: 155.0582,found: 155.0584.

[Preparation Example 69] Preparation of(E)-3-(5-phenylpent-4-en-1-yl)-1,4,2-dioxazol-5-one

Prepared on a 2.6 mmol scale; Colorless oil (0.36 g, 96%); ¹H NMR (600MHz, CDCl₃) δ 7.35 (d, J=7.4 Hz, 2H), 7.31 (t, J=7.2 Hz, 2H), 7.23 (t,J=7.1 Hz, 1H), 6.45 (d, J=15.8 Hz, 1H), 6.15 (dt, J=15.7, 6.9 Hz, 1H),2.68 (t, J=7.4 Hz, 2H), 2.35 (q, J=7.0 Hz, 2H), 1.93 (q, J=7.3 Hz, 2H);¹³C NMR (150 MHz, CDCl₃) δ 166.5, 154.1, 137.0, 132.0, 128.6, 127.7,127.4, 126.0, 31.8, 24.1, 24.1; IR (cm⁻¹) 1868, 1824, 1633, 1146, 965,740; HRMS (EI) m/z calcd. for C₁₃H₁₃NO₃ [M]⁺: 231.0895, found: 231.0896.

[Preparation Example 70] Preparation of3-(4-phenylpent-4-en-1-yl)-1,4,2-dioxazol-5-one

Prepared on a 2.6 mmol scale; Colorless oil (0.58 g, 94%); ¹H NMR (600MHz, CDCl₃) δ 7.40-7.33 (m, 4H), 7.30 (t, J=7.0 Hz, 1H), 5.35 (s, 1H),5.11 (s, 1H), 2.67-2.60 (m, 4H), 1.88 (p, J=8.1, 7.3 Hz, 2H); ¹³C NMR(150 MHz, CDCl₃) δ 166.4, 154.0, 146.3, 140.1, 128.5, 127.8, 126.1,114.0, 34.1, 24.0, 22.7; IR (cm⁻¹) 1870, 1825, 1630, 1147, 979, 704;HRMS (EI) m/z calcd. for C₁₃H₁₃NO₃ [M]⁺: 231.0895, found: 231.0896.

[Preparation Example 71] Preparation of3-(5-phenylpent-4-yn-1-yl)-1,4,2-dioxazol-5-one

Colorless oil (1.0 g, 88%); ¹H NMR (400 MHz, CD₂Cl₂) δ 7.42-7.36 (m,2H), 7.32-7.27 (m, 3H), 2.84 (t, J=7.5 Hz, 2H), 2.58 (t, J=6.7 Hz, 2H),2.02 (p, J=7.0 Hz, 2H); ¹³C NMR (150 MHz, CD₂Cl₂) δ 166.5, 154.2, 131.4,128.3, 127.9, 123.3, 87.4, 82.0, 23.8, 23.5, 18.5; IR (cm⁻¹) 1870, 1823,1634, 1146, 979, 754, 691; HRMS (EI) m/z calcd. for C₁₃H₁₁NO₃ [M]⁺:229.0739, found: 229.0741.

[Preparation Example 72] Preparation of3-(6-phenylhex-4-yn-1-yl)-1,4,2-dioxazol-5-one

Prepared on a 1 mmol scale; Yellow oil (0.18 g, 75%); ¹H NMR (600 MHz,CD₂Cl) δ 7.36-7.28 (m, 4H), 7.23 (t, J=6.5 Hz, 1H), 3.58 (s, 2H), 2.79(t, J=7.5 Hz, 2H), 2.44-2.36 (m, 2H), 1.94 (p, J=7.0 Hz, 2H); ¹³C NMR(150 MHz, CD₂Cl₂) δ 166.5, 154.2, 137.2, 128.4, 127.7, 126.4, 79.8,79.6, 24.9, 23.8, 23.7, 17.9; IR (cm⁻¹) 2939, 1869, 1825, 1636, 1149,982, 760; HRMS (EI) m/z calcd. for C₁₄H₁₃NO₃ [M]⁺: 243.0895, found:243.0899.

[Preparation Example 73] Preparation of3-(hex-4-yn-1-yl)-1,4,2-dioxazol-5-one

Prepared on a 1 mmol scale; Colorless oil (0.16 g, 96%); ¹H NMR (600MHz, CD₂Cl₂) δ 2.77 (t, J=7.5 Hz, 2H), 2.32-2.24 (m, 2H), 1.88 (p, J=6.8Hz, 2H), 1.77 (s, 3H); ¹³C NMR (150 MHz, CD₂Cl₂) δ 166.6, 154.2, 77.3,76.5, 23.8, 23.7, 17.8, 3.0; IR (cm⁻¹) 2920, 1869, 1825, 1634, 1148,982, 759; HRMS (EI) m/z calcd. for C₈H₉NO₃ [M]⁺: 167.0582, found:167.0583.

[Preparation Example 74] Preparation of3-(2-benzylbutyl)-1,4,2-dioxazol-5-one

Prepared on a 1.2 mmol scale; Colorless oil (0.27 g, 96%); ¹H NMR (600MHz, CDCl₃) δ 7.31 (t, J=7.5 Hz, 2H), 7.23 (t, J=7.2 Hz, 1H), 7.16 (d,J=7.5 Hz, 2H), 2.82 (dd, J=13.9, 6.0 Hz, 1H), 2.56-2.50 (m, 3H), 2.12(hept, J=6.6 Hz, 1H), 1.45 (dh, J=14.5, 7.2 Hz, 2H), 1.00 (t, J=7.4 Hz,3H); ¹³C NMR (150 MHz, CDCl₃) 166.0, 154.0, 138.9, 129.1, 128.6, 126.6,39.6, 38.4, 28.2, 26.2, 10.8; IR (cm⁻¹) 2964, 1869, 1826, 1145, 979,699; HRMS (FAB) m/z calcd. for C₁₃H₁₅NO₃ [M+H]⁺: 234.1130, found:234.1133.

[Preparation Example 75] Preparation of3-(2-benzyl-3-methylbutyl)-1,4,2-dioxazol-5-one

Prepared on a 1.2 mmol scale; Colorless oil (0.24 g, 80%); ¹H NMR (400MHz, CD₂Cl₂) δ 7.29 (t, J=7.3 Hz, 2H), 7.24-7.13 (m, 3H), 2.84 (dd,J=13.9, 5.5 Hz, 1H), 2.58 (dd, J=15.7, 6.5 Hz, 1H), 2.52-2.40 (m, 2H),2.15-2.06 (m, 1H), 1.86-1.74 (m, 1H), 0.98 (dd, J=19.0, 6.9 Hz, 6H); ¹³CNMR (150 MHz, CD₂Cl₂) δ 166.6, 154.1, 139.6, 129.0, 128.4, 126.3, 42.8,36.6, 29.7, 26.0, 18.4; IR (cm 1) 2960, 1869, 1825, 1631, 980, 699; HRMS(FAB) m/z calcd. for C₁₄H₁₇NO₃ [M+H]⁺: 248.1287, found: 248.1285.

[Preparation Example 76] Preparation of(S)-2-(3-methyl-1-(5-oxo-1,4,2-dioxazol-3-yl)butyl)isoindoline-1,3-dione

White solid (0.93 g, 62%); ¹H NMR (400 MHz, CDCl₃) δ 7.91 (dd, J=5.5,3.1 Hz, 2H), 7.80 (dd, J=5.5, 3.1 Hz, 2H), 5.43 (dd, J=10.7, 4.7 Hz,1H), 2.48-2.37 (m, 1H), 1.98 (ddd, J=14.3, 9.6, 4.7 Hz, 1H), 1.67-1.56(m, 1H), 0.99 (dd, J=8.8, 6.6 Hz, 6H); ¹³C NMR (150 MHz, CDCl₃) δ 166.8,164.3, 153.3, 134.8, 131.2, 124.0, 43.7, 36.4, 24.5, 22.8, 21.2; IR(cm⁻¹) 2959, 2924, 2876, 1830, 1716, 1380, 989, 756, 711; HRMS (EI) m/zcalcd. for C₁₅H₁₄N₂O₅ [M]⁺: 302.0903, found: 302.0904.

[Preparation Example 77] Preparation of(S)-2-(1-(5-oxo-1,4,2-dioxazol-3-yl)-3-phenylpropyl)isoindoline-1,3-dione

Prepared on a 2.0 mmol scale; White solid (0.44 g, 62%); ¹H NMR (400MHz, CDCl₃) δ 7.86 (dd, J=5.5, 3.0 Hz, 2H), 7.78 (dd, J=5.5, 3.1 Hz,2H), 7.20 (t, J=7.5 Hz, 2H), 7.14 (d, J=6.6 Hz, 2H), 7.08 (t, J=7.2 Hz,1H), 5.36 (t, J=4.8 Hz, 1H), 2.85-2.73 (m, 3H), 2.61-2.52 (m, 1H); ¹³CNMR (150 MHz, CDCl₃) δ 166.7, 163.9, 153.3, 138.9, 134.7, 131.2, 128.6,128.3, 126.4, 123.9, 44.9, 31.8, 28.9; IR (cm⁻¹) 1834, 1781, 1716, 1381,754; HRMS (EI) m/z calcd. for C₁₉H₁₄N₂O₅ [M]⁺: 350.0903, found:350.0900.

[Preparation Example 78] Preparation of(R)-2-(3-Methyl-1-(5-oxo-1,4,2-dioxazol-3-yl)butan-2-yl)isoindoline-1,3-dione

Prepared on a 2.0 mmol scale; White solid(0.22 g, 38%); ¹H NMR (400 MHz,CDCl₃) δ 7.85-7.79 (m, 2H), 7.76-7.70 (m, 2H), 4.23 (ddd, J=10.9, 9.9,3.5 Hz, 1H), 3.60 (dd, J=16.0, 11.0 Hz, 1H), 3.08 (dd, J=16.0, 3.6 Hz,1H), 2.57-2.41 (m, 1H), 1.10 (d, J=6.7 Hz, 3H), 0.88 (d, J=6.7 Hz, 3H);¹³C NMR (100 MHz, CDCl₃) δ 168.2, 164.7, 153.7, 134.5, 131.3, 123.7,53.8, 30.4, 25.8, 20.2, 19.7; IR (cm⁻¹) 2967, 1865, 1828, 1703, 979,719; HRMS (EI) m/z calcd. for C₁₅H₁₄N₂O₅ [M]⁺: 302.0903, found:302.0904.

[Preparation Example 79] Preparation of2-((1-((5-oxo-1,4,2-dioxazol-3-yl)methyl)cyclohexyl)methyl)isoindoline-1,3-dione

Prepared on a 2.0 mmol scale; White solid (0.36 g, 52%); ¹H NMR (400MHz, CDCl₃) δ 7.84 (dd, J=5.5, 3.1 Hz, 2H), 7.74 (dd, J=5.5, 3.1 Hz,2H), 3.76 (s, 2H), 2.72 (s, 2H), 1.74-1.63 (m, 2H), 1.52-1.42 (m, 8H);¹³C NMR (100 MHz, CDCl₃) δ 169.2, 165.2, 154.1, 134.4, 131.8, 123.6,45.4, 38.7, 33.5, 32.0, 25.4, 21.4; IR (cm⁻¹) 2922, 1824, 1707, 1390,984, 711; HRMS (EI) m/z calcd. for C₁₈H₁₈N₂O₅ [M]⁺: 342.1216, found:342.1212.

[Preparation Example 80] Preparation of tert-butyl([1-{(5-oxo-1,4,2-dioxazol-3-yl)methyl}cyclohexyl]methyl)carbamate

Prepared at 1.0 mmol scale; Colorless oil (0.23 g, 75%); ¹H NMR (400MHz, Methylene Chloride-d₂) δ 4.78 (s, 1H), 3.14 (d, J=6.9 Hz, 2H), 2.62(s, 2H), 1.62-1.33 (m, 19H); ¹³C NMR (100 MHz, Methylene Chloride-d₂) δ165.5, 156.1, 154.1, 79.1, 46.5, 38.1, 33.3, 31.3, 28.0, 25.6, 21.3; IR(cm⁻¹) 3349, 2929, 1829, 1698, 1628, 1510, 1455, 1365, 1246, 1163, 983,763; HRMS (FAB) m/z calcd. for C₁₅H₂₄N₂O₅ [M+H]⁺: 313.1763, found:313.1760.

[Preparation Example 81] Preparation ofanti-(Z)-3-((3-oxo-2-(pent-2-en-1-yl)cyclopentyl)methyl)-1,4,2-dioxazol-5-one

Prepared on a 1.8 mmol scale; Colorless oil (0.34 g, 77%); ¹H NMR (600MHz, CDCl₃) δ 5.53-5.47 (m, 1H), 5.23 (q, J=8.7, 8.2 Hz, 1H), 3.04 (dd,J=15.6, 4.3 Hz, 1H), 2.63 (dd, J=15.6, 9.2 Hz, 1H), 2.49-2.24 (m, 6H),2.20-2.13 (m, 1H), 2.05 (p, J=7.4 Hz, 2H), 1.98-1.93 (m, 1H), 1.62-1.54(m, 1H), 0.97 (t, J=7.6 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 216.8,165.1, 153.7, 134.8, 124.3, 53.8, 37.8, 37.4, 29.6, 27.0, 25.7, 20.6,14.0; IR (cm⁻¹) 2963, 1870, 1826, 1736, 1147, 979; HRMS (EI) m/z calcd.for C₁₃H₁₇NO₄ [M]⁺: 251.1158, found: 251.1155.

[Preparation Example 82] Preparation of3-((3R)-3-((3R,8R,9S,10S,13R,14S,17R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)butyl)-1,4,2-dioxazol-5-one

Prepared on a 3.0 mmol scale; White solid (1.23 g, 95%); ¹H NMR (600MHz, CDCl₃) δ 3.35 (s, 3H), 3.16 (dt, J=10.9, 5.6 Hz, 1H), 2.66 (ddd,J=15.2, 7.4, 3.4 Hz, 1H), 2.57-2.48 (m, 1H), 1.94 (d, J=12.4 Hz, 1H),1.89-1.81 (m, 3H), 1.81-1.73 (m, 2H), 1.68 (q, J=12.7, 12.2 Hz, 1H),1.59 (d, J=11.8 Hz, 2H), 1.50-1.34 (m, 7H), 1.28-1.21 (m, 4H), 1.09 (dt,J=33.9, 8.7 Hz, 5H), 0.97 (d, J=6.4 Hz, 3H), 0.94-0.92 (m, 4H), 0.65 (s,3H); ¹³C NMR (150 MHz, CDCl₃) δ 167.1, 154.2, 80.4, 56.4, 55.6, 55.5,42.8, 42.0, 40.3, 40.1, 35.8, 35.3, 35.2, 34.9, 32.7, 30.6, 28.2, 27.3,26.8, 26.3, 24.1, 23.4, 21.8, 20.8, 18.0, 12.0; IR (cm 1) 2923, 2865,1856, 1822, 1634, 1091, 982; HRMS (EI) m/z calcd. for C₂₆H₄₁NO₄ [M]⁺:431.3036, found: 431.3033.

[Preparation Example 83] Preparation of3-(2,6-dimethylhept-5-en-1-yl)-1,4,2-dioxazol-5-one

Prepared on a 3.2 mmol scale; Colorless oil (577 mg, 85%); ¹H NMR (600MHz, CDCl₃) δ 5.06 (t, J=7.0 Hz, 1H), 2.61 (dd, J=15.2, 5.8 Hz, 1H),2.45 (dd, J=15.2, 8.1 Hz, 1H), 2.00 (tdd, J=27.5, 14.1, 7.0 Hz, 3H),1.69 (s, 3H), 1.61 (s, 3H), 1.42 (td, J=14.7, 6.3 Hz, 1H), 1.32 (dt,J=13.7, 7.2 Hz, 1H), 1.02 (d, J=6.7 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ166.1, 154.2, 132.4, 123.3, 36.3, 31.7, 29.8, 25.7, 25.1, 19.3, 17.7; IR(cm⁻¹) 2961, 1875, 1828, 1632, 1145, 979, 761; HRMS (EI) m/z calcd. forC₁₁H₁₇NO₃ [M]⁺: 211.1208, found: 211.1209.

[Preparation Example 84] Preparation of3-((S)-1-((2R,4aS)-4a,8-dimethyl-7-oxo-1,2,3,4,4a,7-hexahydronaphthalen-2-yl)ethyl)-1,4,2-dioxazol-5-one

Prepared on a 1 mmol scale; White solid (0.14 g, 48%); ¹H NMR (400 MHz,acetone-d₆) δ 6.85 (d, J=9.9 Hz, 1H), 6.09 (d, J=9.9 Hz, 1H), 3.14-3.04(m, 1H), 2.95-2.85 (m, 1H), 2.24 (t, J=12.7 Hz, 1H), 1.98-1.89 (m, 1H),1.87-1.69 (m, 6H), 1.42-1.27 (m, 4H), 1.24 (s, 3H); ¹³C NMR (100 MHz,acetone-d₆) δ 185.8, 169.7, 158.9, 157.1, 155.3, 130.0, 126.6, 42.1,40.8, 38.1, 36.8, 31.8, 24.3, 23.7, 13.3, 10.5; IR (cm⁻¹) 2979, 2949,2919, 1822, 1658, 1625, 980, 839; HRMS (EI) m/z calcd. for C₁₆H₁₉NO₄[M]⁺: 289.1314, found: 289.1312.

Example II: Preparation of Gamma-Lactam Compound from Dioxazol-OneCompound [Example 14] Preparation of 5-phenylpyrrolidin-2-one (1)

Metal complex J (2.4 mg, 2.0 mol %), sodium tetrakis [3,5-bis(trifluoromethyl)phenyl]borate (NaBAr^(F) ₄, 4.5 mg, 2.0 mol %), anddichloromethane (2.4 mL) were added to a well-dried vial under an argonatmosphere, the mixture was stirred for 1 minute,3-(3-phenylpropyl)-1,4,2-dioxazol-5-one (10.3 mg, 0.2 mmol) was addedthereto, and the vial was sealed under an argon atmosphere. Thereafter,the reaction mixture was vigorously stirred at 40° C. for 12 hours,cooled to room temperature, filtered with celite, washed withdichloromethane (5 mL×4), and concentrated under reduced pressure. Theconcentrated residue was separated and purified with columnchromatography (eluent: n-hexane/10% methanol-EtOAc solution, 2:1˜1:1)to obtain the desired compound (35 mg, 95%).

5-Phenylpyrrolidin-2-one (1)

Catalyst J (2.4 mg, 2 mol %) was used. White solid (31 mg, 95%); ¹H NMR(600 MHz, CDCl₃) δ 7.38-7.33 (m, 2H), 7.32-7.27 (m, 3H), 6.57 (br, 1H),4.75 (t, J=7.1 Hz, 1H), 2.60-2.52 (m, 1H), 2.49-2.35 (m, 2H), 2.00-1.92(m, 1H); ¹³C NMR (150 MHz, CDCl₃) δ 178.6, 142.5, 128.9, 127.8, 125.6,58.1, 31.3, 30.3.

Gamma-lactam compounds having various structures were prepared in thesame manner as in Example 14, except that the starting material, thereaction temperature, the catalyst, or the base was different, and thesynthesis data of the prepared gamma-lactam compounds are shown in thefollowing.

[Example 15] Preparation of 5-(4-bromophenyl)pyrrolidin-2-one (2)

Catalyst J (2.4 mg, 2 mol %) was used. White solid (45 mg, 94%); m.p.147-149° C.; ¹H NMR (600 MHz, CDCl₃) δ 7.50 (d, J=8.4 Hz, 2H), 7.18 (d,J=8.3 Hz, 2H), 6.00 (s, 1H), 4.72 (t, J=7.1 Hz, 1H), 2.58 (dtd, J=12.8,8.4, 7.8, 4.9 Hz, 1H), 2.45 (ddp, J=25.9, 17.2, 9.0 Hz, 2H), 1.93 (dt,J=15.8, 8.1 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃) δ 178.1, 141.5, 132.0,127.3, 121.8, 57.4, 31.3, 30.0; IR (cm⁻¹) 3175, 3074, 1677, 1262, 1008,789; HRMS (EI) m/z calcd. for C₁₀H₁₀BrNO [M]⁺: 238.9946, found:238.9943.

[Example 16] Preparation of 5-(4-fluorophenyl)pyrrolidin-2-one (3)

Catalyst J (2.4 mg, 2 mol %) was used. White solid (31 mg, 87%); m.p.135-137° C.; ¹H NMR (600 MHz, CDCl₃) δ 7.26-7.21 (m, 2H), 7.10 (s, 1H),7.05-6.98 (m, 2H), 4.72 (t, J=7.1 Hz, 1H), 2.56-2.46 (m, 1H), 2.46-2.30(m, 2H), 1.93-1.85 (m, 1H); ¹³C NMR (150 MHz, CDCl₃) δ 178.9, 162.4 (d,J=246.1 Hz), 138.4 (d, J=3.2 Hz), 127.4 (d, J=8.2 Hz), 115.8 (d, J=21.6Hz), 57.7, 31.4, 30.5; ¹⁹F NMR (564 MHz, CDCl₃) δ −114.7 (m); IR (cm⁻¹)3167, 3084, 1682, 1509, 1217, 793, 482; HRMS (EI) m/z calcd. forC₁₀H₁₀FNO [M]⁺: 179.0746, found: 179.0745.

[Example 17] Preparation of 5-(4-nitrophenyl)pyrrolidin-2-one (4)

Catalyst J (2.4 mg, 2 mol %) was used. White solid (35 mg, 85%); m.p.141-143° C.; ¹H NMR (600 MHz, CDCl₃) δ 8.24 (d, J=8.6 Hz, 2H), 7.49 (d,J=8.6 Hz, 2H), 6.75 (s, 1H), 4.89 (t, J=7.2 Hz, 1H), 2.70-2.62 (m, 1H),2.53-2.41 (m, 2H), 1.95 (dq, J=15.7, 8.5 Hz, 1H); ¹³C NMR (150 MHz,CDCl₃, one carbon merged to others) δ 149.9, 147.6, 126.4, 124.2, 57.4,31.0, 30.2; IR (cm⁻¹) 3067, 1678, 1520, 1338; HRMS (EI) m/z calcd. forC₁₀H₁₀N₂O₃[M]: 206.0691, found: 206.0688.

[Example 18] Preparation of 5-(4-methoxyphenyl)pyrrolidin-2-one (5)

Catalyst J (2.4 mg, 2 mol %) was used. White solid (26 mg, 68%); m.p.128-130° C.; ¹H NMR (600 MHz, CDCl₃) δ 7.21 (d, J=8.3 Hz, 2H), 6.89 (d,J=8.2 Hz, 2H), 6.08 (s, 1H), 4.70 (t, J=7.2 Hz, 1H), 3.80 (s, 3H),2.56-2.34 (m, 3H), 1.95 (dq, J=15.8, 8.3 Hz, 1H); ¹³C NMR (150 MHz,CDCl₃) δ 178.2, 159.3, 134.4, 126.9, 114.2, 57.6, 55.3, 31.6, 30.5; IR(cm⁻¹) 3179, 2918, 1681, 1515, 1241, 1022; HRMS (EI) m/z calcd. forC₁₁H₁₃NO₂ [M]⁺: 191.0946, found: 191.0946.

[Example 19] Preparation of tert-butyl{4-(5-oxopyrrolidin-2-yl)phenyl}carbamate (6)

Catalyst J (11.8 mg, 10 mol %) and NaBAr^(F) ₄ (17.6 mg, 10 mol %) wereused at 40° C. for 12 hours and further at 80° C. for 36 hours. Whitesolid (36 mg, 67%); m.p. 201-203° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.36 (d,J=8.2 Hz, 2H), 7.21 (d, J=8.6 Hz, 2H), 6.59 (s, 1H), 5.92 (s, 1H), 4.70(t, J=7.1 Hz, 1H), 2.59-2.50 (m, 1H), 2.49-2.34 (m, 2H), 2.00-1.88 (m,1H), 1.51 (s, 9H); ¹³C NMR (150 MHz, CDCl₃) δ 178.2, 152.7, 138.2,136.8, 126.3, 119.0, 80.7, 57.6, 31.5, 30.3, 28.3; IR (cm⁻¹) 2968, 1782,1746, 1718, 1271; HRMS (FAB) m/z calcd. for C₁₅H₂₀N₂O₃[M+H]⁺: 277.1552,found: 277.1550.

[Example 20] Preparation of 3,3-dimethyl-5-phenylpyrrolidin-2-one (7)

Catalyst J (11.8 mg, 10 mol %) and NaBAr^(F) ₄ (17.7 mg, 10 mol %) wereused at 80° C. White solid (20 mg, 53%); m.p. 161-163° C.; ¹H NMR (600MHz, CDCl₃) δ 7.37 (t, J=7.5 Hz, 2H), 7.31 (d, J=7.5 Hz, 3H), 5.85 (s,1H), 4.68 (t, J=7.8 Hz, 1H), 2.38 (dd, J=12.8, 6.9 Hz, 1H), 1.84 (dd,J=12.8, 8.6 Hz, 1H), 1.26 (s, 3H), 1.22 (s, 3H); ¹³C NMR (150 MHz,CDCl₃) δ 182.6, 142.3, 128.9, 127.9, 125.7, 54.7, 47.4, 25.1, 24.5; IR(cm⁻¹) 3169, 3076, 2968, 2924, 1677, 1260, 701; HRMS (EI) m/z calcd. forC₁₂H₁₅NO [M]⁺: 189.1154, found: 189.1152.

[Example 21] Preparation of 3-methyl-5-phenylpyrrolidin-2-one (8)

Using Catalyst K (2.4 mg, 2 mol %). White solid (19 mg, 53%); ¹H NMRspectroscopic analysis of the unpurified reaction mixture represented1:0.8 dr.

cis-3-Methyl-5-phenylpyrrolidin-2-one (8-A)

Major diastereomer: m.p. 101-103° C.; ¹H NMR (600 MHz, CDCl₃) δ7.40-7.34 (m, 2H), 7.33-7.28 (m, 3H), 5.85 (s, 1H), 4.69-4.59 (m, 1H),2.77-2.66 (m, 1H), 2.65-2.52 (m, 1H), 1.66-1.55 (m, 1H), 1.25 (d, J=7.0Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 180.4, 142.2, 129.1, 128.2, 126.0,56.6, 41.2, 37.3, 15.9; IR (cm⁻¹) 3193, 2926, 1682, 1284, 758, 697, 482;HRMS (EI) m/z calcd. for C₁₁H₁₃NO [M]⁺: 175.0997, found: 175.0996.

trans-3-Methyl-5-phenylpyrrolidin-2-one (8-B)

Minor diastereomer: m.p. 120-122° C.; ¹H NMR (400 MHz, CDCl₃) δ7.40-7.33 (m, 2H), 7.33-7.25 (m, 3H), 6.00 (s, 1H), 4.77-4.69 (m, 1H),2.70-2.54 (m, 1H), 2.31-2.15 (m, 2H), 1.25 (d, J=7.2 Hz, 3H); ¹³C NMR(100 MHz, CDCl₃) δ 181.1, 142.8, 129.0, 127.9, 125.6, 55.7, 39.6, 34.9,16.1; IR (cm⁻¹) 3224, 2969, 1680, 1283, 737, 698; HRMS (ESI) m/z calcd.for C₁₁H₁₃NO [M+H]⁺: 176.1070, found: 176.1062.

[Example 22] Preparation of trans-4-methyl-5-phenylpyrrolidin-2-one (9)

Catalyst J (2.4 mg, 2 mol %) was used. White solid (35 mg, 99%); ¹H NMRspectroscopic analysis of the unpurified reaction mixtureindicated >20:1 dr; m.p. 116-118° C.; ¹H NMR (600 MHz, CDCl₃) δ 7.37 (t,J=7.3 Hz, 2H), 7.34-7.29 (m, 3H), 5.90 (br, 1H), 4.22 (d, J=7.3 Hz, 1H),2.61 (dd, J=16.7, 8.2 Hz, 1H), 2.30 (dp, J=14.7, 6.8 Hz, 1H), 2.13 (dd,J=16.7, 9.5 Hz, 1H), 1.16 (d, J=6.7 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ177.3, 141.0, 128.8, 128.1, 126.1, 65.9, 40.6, 38.8, 17.7; IR (cm⁻¹)3175, 2966, 1674, 1340, 751, 702; HRMS (EI) m/z calcd. for C₁₁H₁₃NO[M]⁺: 175.0997, found: 175.0995.

[Example 23] Preparation ofcis-3,3a,4,8b-tetrahydroindeno[1,2-b]pyrrol-2(1H)-one (10)

Catalyst J (2.4 mg, 2 mol %) was used. White solid (34 mg, 99%); ¹H NMRspectroscopic analysis of the unpurified reaction mixtureindicated >20:1 dr; m.p. 215-217° C.; ¹H NMR (600 MHz, CDCl₃) δ7.30-7.22 (m, 4H), 6.48 (br, 1H), 5.02 (d, J=6.9 Hz, 1H), 3.35-3.27 (m,2H), 2.90-2.83 (m, 1H), 2.71 (dd, J=17.3, 9.2 Hz, 1H), 2.22 (dd, J=17.4,4.6 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃) δ 177.4, 142.5, 141.5, 128.7,127.2, 125.4, 124.7, 63.2, 38.5, 37.6, 37.4; IR (cm⁻¹) 3207, 1692, 1645,748; HRMS (EI) m/z calcd. for C₁₁H₁₁NO [M]⁺: 173.0841, found: 173.0842.

[Example 24] Preparation of 3-methylisoindolin-1-one (11)

Using Catalyst K (5.9 mg, 5 mol %) and NaBAr^(F) ₄ (8.8 mg, 5 mol %).White solid (22 mg, 75%); m.p. 114-116° C.; ¹H NMR (600 MHz, CDCl₃) δ7.85 (d, J=7.6 Hz, 1H), 7.58 (t, J=7.9 Hz, 1H), 7.47 (t, J=7.5 Hz, 1H),7.43 (d, J=8.0 Hz, 1H), 6.75 (s, 1H), 4.70 (q, J=6.8 Hz, 1H), 1.51 (d,J=6.7 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 170.5, 148.8, 131.9, 131.4,128.1, 123.8, 122.2, 52.4, 20.3; IR (cm⁻¹) 3219, 1693, 1655, 721, 682;HRMS (EI) m/z calcd. for C₉H₉NO [M]⁺: 147.0684, found: 147.0685.

[Example 25] Preparation of 3-phenylisoindolin-1-one (12)

Catalyst J (5.9 mg, 5 mol %) and NaBAr^(F) ₄ (8.8 mg, 5 mol %) wereused. White solid (37 mg, 88%); m.p. 216-218° C.; ¹H NMR (600 MHz,CDCl₃) δ 7.89 (d, J=7.3 Hz, 1H), 7.49 (dt, J=21.2, 7.3 Hz, 2H),7.38-7.31 (m, 3H), 7.28-7.25 (m, 2H), 7.23 (d, J=7.4 Hz, 1H), 6.63 (s,1H), 5.62 (s, 1H); ¹³C NMR (150 MHz, CDCl₃) δ 170.9, 147.9, 138.4,132.3, 130.7, 129.1, 128.5, 128.3, 126.8, 123.8, 123.3, 60.7; IR (cm⁻¹)3172, 3055, 2855, 1680, 740, 695; HRMS (EI) m/z calcd. for C₁₄H₁₁NO[M]⁺: 209.0841, found: 209.0842.

[Example 26] Preparation of 5-(benzofuran-2-yl)pyrrolidin-2-one (13)

Catalyst J (11.8 mg, 10 mol %) and NaBAr^(F) ₄ (17.7 mg, 10 mol %) wereused. White solid (37 mg, 92%); m.p. 122-124° C.; ¹H NMR (600 MHz,CDCl₃) δ 7.53 (d, J=7.7 Hz, 1H), 7.45 (d, J=8.2 Hz, 1H), 7.30-7.26 (m,1H), 7.23 (t, J=7.5 Hz, 1H), 6.61 (s, 1H), 6.30 (s, 1H), 4.91 (dd,J=7.6, 4.7 Hz, 1H), 2.62-2.54 (m, 2H), 2.46-2.39 (m, 1H), 2.38-2.31 (m,1H); ¹³C NMR (150 MHz, CDCl₃) δ 178.0, 157.1, 155.0, 127.8, 124.5,123.0, 121.0, 111.2, 102.8, 51.7, 29.3, 26.9; IR (cm⁻¹) 3193, 3072,1688, 1257, 812, 743; HRMS (EI) m/z calcd. for C₁₂H₁₁NO₂ [M]⁺: 201.0790,found: 201.0790.

[Example 27] Preparation of 5-(thiophen-2-yl)pyrrolidin-2-one (14)

Catalyst J (11.8 mg, 10 mol %) and NaBAr^(F) ₄ (17.7 mg, 10 mol %) wereused at 80° C. White solid (28 mg, 84%); m.p. 112-114° C.; ¹H NMR (600MHz, CDCl₃) δ 7.30-7.22 (m, 1H), 7.02-6.94 (m, 2H), 6.32 (s, 1H), 5.03(t, J=6.8 Hz, 1H), 2.66-2.48 (m, 2H), 2.48-2.35 (m, 1H), 2.20-2.08 (m,1H); ¹³C NMR (150 MHz, CDCl₃) δ 177.7, 146.4, 126.9, 124.8, 124.1, 53.8,31.7, 30.0; IR (cm⁻¹) 3165, 3069, 1677, 1260, 784, 698, 481; HRMS (EI)m/z calcd. for C₈H₉NOS [M]⁺: 167.0405, found: 167.0404.

[Example 28] Preparation of 5,5-dimethylpyrrolidin-2-one (15)

Catalyst J (2.4 mg, 2 mol %) was used. White solid (20 mg, 88%); ¹H NMR(600 MHz, CDCl₃) δ 6.35 (s, 1H), 2.40 (t, J=7.9 Hz, 2H), 1.91 (t, J=7.9Hz, 2H), 1.28 (s, 6H); ¹³C NMR (150 MHz, CDCl₃) δ 177.0, 56.5, 35.3,30.6, 29.2.

[Example 29] Preparation of 1-azaspiro[4.5]decan-2-one (16)

Catalyst J (2.4 mg, 2 mol %) was used. White solid (23 mg, 75%); m.p.126-128° C.; ¹H NMR (600 MHz, CDCl₃) 6.56 (s, 1H), 2.37 (t, J=8.1 Hz,2H), 1.90 (t, J=8.1 Hz, 2H), 1.57-1.48 (m, 8H), 1.44-1.38 (m, 2H); ¹³CNMR (150 MHz, CDCl₃) δ 177.1, 59.2, 38.3, 32.7, 29.8, 25.1, 23.0; IR(cm⁻¹) 3209, 2929, 1683, 1264, 731, 701; HRMS (EI) m/z calcd. forC₉H₁₅NO [M]⁺: 153.1154, found: 153.1156.

[Example 30] Preparation of 3,3-dimethylisoindolin-1-one (17)

Prepared with Catalyst J (5.9 mg, 5 mol %) and NaBAr^(F) ₄ (8.8 mg, 5mol %). White solid (30 mg, 94%); m.p. 160-162° C.; ¹H NMR (600 MHz,CDCl₃) δ 7.82 (d, J=7.6 Hz, 1H), 7.56 (t, J=7.5 Hz, 1H), 7.44 (t, J=7.5Hz, 1H), 7.40 (d, J=7.7 Hz, 1H), 7.01 (s, 1H), 1.56 (s, 6H); ¹³C NMR(150 MHz, CDCl₃) δ 169.6, 153.0, 132.0, 130.6, 128.0, 123.8, 120.8,59.0, 27.8; IR (cm⁻¹) 3199, 2967, 1689, 1264, 732; HRMS (EI) m/z calcd.for C₁₀H₁₁NO [M]⁺: 161.0841, found: 161.0839.

[Example 31] Preparation of (R)-5-ethyl-5-methylpyrrolidin-2-one (18)

Catalyst J (2.4 mg, 2 mol %) was used. Colorless oil (21 mg, 83%); ¹HNMR (400 MHz, CDCl₃) δ 6.86 (s, 1H), 2.44-2.28 (m, 2H), 1.93 (ddd,J=12.8, 8.9, 7.3 Hz, 1H), 1.80 (ddd, J=12.9, 9.2, 7.0 Hz, 1H), 1.57-1.46(m, 2H), 1.21 (s, 3H), 0.89 (t, J=7.5 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃)δ 177.5, 59.6, 34.6, 32.9, 30.6, 26.7, 8.4; IR (cm⁻¹) 3207, 2965, 1683,1380; HRMS (FAB) m/z calcd. for C₇H₁₃NO [M+H]⁺: 128.1075, found:128.1077; Optical Rotation: [α]_(D)=−11.8 (c=1.0, benzene).

[Example 32] Preparation of 5-methylpyrrolidin-2-one (19)

Using Catalyst K (5.9 mg, 5 mol %) and NaBAr^(F) ₄ (8.8 mg, 5 mol %). ¹HNMR (400 MHz, CDCl₃) δ 6.37 (s, 1H), 3.78 (q, J=6.4 Hz, 1H), 2.41-2.20(m, 3H), 1.72-1.59 (m, 1H), 1.22 (d, J=6.2 Hz, 3H); ¹³C NMR (150 MHz,CDCl₃) 178.1, 50.0, 30.5, 29.2, 22.2.

[Example 33] Preparation of cis-hexahydrocyclopenta[b]pyrrol-2(1H)-one(20)

Using Catalyst K (5.9 mg, 5 mol %) and NaBAr^(F) ₄ (8.8 mg, 5 mol %).White solid (18 mg, 72%); ¹H NMR spectroscopic analysis of theunpurified reaction mixture indicated >20:1 dr; m.p. 53-55° C.; ¹H NMR(600 MHz, CDCl₃) δ 5.87 (s, 1H), 4.14-4.04 (m, 1H), 2.83 (q, J=8.3, 7.7Hz, 1H), 2.63 (dd, J=17.6, 10.3 Hz, 1H), 2.11-2.00 (m, 1H), 1.79 (dt,J=13.9, 7.8 Hz, 1H), 1.72-1.60 (m, 4H), 1.56-1.48 (m, 1H); ¹³C NMR (150MHz, CDCl₃) δ 178.1, 59.1, 37.8, 37.3, 34.5, 34.3, 23.7; IR (cm⁻¹) 3221,2953, 1683, 730; HRMS (EI) m/z calcd. for C₇H₁₁NO [M]⁺: 125.0841, found:125.0842.

[Example 34] Preparation ofoctahydro-3a,7:5,9-dimethanocycloocta[b]pyrrol-2(3H)-one (21)

Using Catalyst K (5.9 mg, 5 mol %) and NaBAr^(F) ₄ (8.8 mg, 5 mol %).White solid (35 mg, 91%); m.p. 161-163° C.; ¹H NMR (600 MHz, CDCl₃) δ5.70 (s, 1H), 3.47 (s, 1H), 2.11-2.01 (m, 3H), 1.93-1.87 (m, 3H), 1.84(d, J=11.9 Hz, 2H), 1.80 (d, J=12.8 Hz, 1H), 1.76-1.70 (m, 3H), 1.67 (d,J=12.4 Hz, 1H), 1.61 (d, J=12.7 Hz, 1H), 1.42 (d, J=11.4 Hz, 1H); ¹³CNMR (150 MHz, CDCl₃) δ 178.9, 63.9, 46.2, 40.0, 38.5, 37.1, 37.0, 36.7,29.5, 29.4, 28.9, 27.3; IR (cm⁻¹) 3172, 2910, 2851, 1682, 733; HRMS (EI)m/z calcd. for C₁₂H₁₇NO [M]⁺: 191.1310, found: 191.1307.

[Example 35] Preparation of 4,4-dimethylpyrrolidin-2-one (22)

Using Catalyst K (5.9 mg, 5 mol %) and NaBAr^(F) ₄ (8.8 mg, 5 mol %) ina solvent of hexafluoro-2-propanol (2.4 mL). Yellowish oil (7 mg, 31%);¹H NMR (600 MHz, CDCl₃) δ 6.04 (s, 1H), 3.11 (s, 2H), 2.14 (s, 2H), 1.17(s, 6H); ¹³C NMR (150 MHz, CDCl₃) δ 178.0, 55.4, 45.2, 35.9, 27.7; IR(cm⁻¹) 3233, 2956, 2868, 1686, 1311, 1249; HRMS (FAB) m/z calcd. forC₆H₁₁NO [M+H]⁺: 114.0919, found: 114.0917.

[Example 36] Preparation of 5-vinylpyrrolidin-2-one (23)

Using Catalyst K (11.8 mg, 10 mol %) and NaBAr^(F) ₄ (17.7 mg, 10 mol%). Colorless resin (14 mg, 63%); ¹H NMR (600 MHz, CDCl₃) δ 6.40 (s,1H), 5.79 (ddd, J=16.9, 10.2, 6.6 Hz, 1H), 5.21 (dd, J=16.9, 1.3 Hz,1H), 5.11 (dd, J=10.3, 1.4 Hz, 1H), 4.15 (q, J=6.6 Hz, 1H), 2.42-2.26(m, 3H), 1.88-1.77 (m, 1H); ¹³C NMR (150 MHz, CDCl₃) δ 178.4, 138.7,115.7, 56.7, 29.8, 28.0.

[Example 37] Preparation of 5-(1-phenylvinyl)pyrrolidin-2-one (24)

Catalyst J (11.8 mg, 10 mol %) and NaBAr^(F) ₄ (17.7 mg, 10 mol %) wereused. White solid (18 mg, 48%); m.p. 104-106° C.; ¹H NMR (600 MHz,CDCl₃) δ 7.37-7.30 (m, 5H), 6.56 (s, 1H), 5.35 (s, 1H), 5.28 (s, 1H),4.70 (t, J=6.0 Hz, 1H), 2.42-2.29 (m, 3H), 1.84 (tt, J=10.2, 5.6 Hz,1H); ¹³C NMR (150 MHz, CDCl₃) δ 178.6, 149.1, 138.9, 128.6, 128.0,126.5, 111.5, 56.7, 29.4, 27.8; IR (cm⁻¹) 3203, 1684, 766, 700; HRMS(EI) m/z calcd. for C₁₂H₁₃NO [M]⁺: 187.0997, found: 187.0996.

[Example 38] Preparation of (E)-5-Styrylpyrrolidin-2-one (25)

Catalyst J (11.8 mg, 10 mol %) and NaBAr^(F) ₄ (17.7 mg, 10 mol %) wereused. White solid (33 mg, 88%); m.p. 101-103° C.; ¹H NMR (400 MHz,CDCl₃) δ 7.39-7.30 (m, 4H), 7.27 (t, J=7.4 Hz, 1H), 6.55 (d, J=15.8 Hz,1H), 6.13 (dd, J=15.8, 7.4 Hz, 1H), 5.87 (s, 1H), 4.40-4.28 (m, 1H),2.47-2.32 (m, 3H), 2.01-1.87 (m, 1H); ¹³C NMR (150 MHz, CDCl₃) δ 178.0,136.0, 131.2, 129.8, 128.7, 128.0, 126.5, 56.4, 29.9, 28.5; IR (cm⁻¹)3214, 3024, 1684, 965, 749, 692; HRMS (EI) m/z calcd. for C₁₂H₁₃NO [M]⁺:187.0997, found: 187.0995.

[Example 39] Preparation of 5-(phenylethynyl)pyrrolidin-2-one (26)

Catalyst J (11.8 mg, 10 mol %) and NaBAr^(F) ₄ (17.7 mg, 10 mol %) wereused. White solid (34 mg, 92%); m.p. 99-101° C.; ¹H NMR (600 MHz, CDCl₃)δ 7.41 (dd, J=7.7, 1.7 Hz, 2H), 7.34-7.29 (m, 3H), 5.84 (s, 1H), 4.62(dd, J=7.5, 5.1 Hz, 1H), 2.57-2.50 (m, 2H), 2.40-2.34 (m, 1H), 2.34-2.27(m, 1H); ¹³C NMR (150 MHz, CDCl₃) δ 177.3, 131.6, 128.6, 128.3, 122.1,87.8, 84.1, 45.2, 29.4, 29.2; IR (cm⁻¹) 3176, 3066, 1693, 1335, 1257,754; HRMS (EI) m/z calcd. for C₁₂H₁₁NO [M]⁺: 185.0841, found: 185.0838.

[Example 40] Preparation of 5-(3-phenylprop-1-yn-1-yl)pyrrolidin-2-one(27)

Catalyst J (11.8 mg, 10 mol %) and NaBAr^(F) ₄ (17.7 mg, 10 mol %) wereused. Yellow resin (30 mg, 75%); ¹H NMR (600 MHz, CDCl₃) δ 7.35-7.26 (m,4H), 7.27-7.20 (m, 1H), 6.59 (s, 1H), 4.46-4.34 (m, 1H), 3.58 (s, 2H),2.49-2.36 (m, 2H), 2.34-2.24 (m, 1H), 2.20-2.11 (m, 1H); ¹³C NMR (150MHz, CDCl₃) δ 177.9, 136.3, 128.7, 127.9, 126.8, 82.2, 81.4, 45.2, 29.7,29.4, 25.1; IR (cm⁻¹) 3229, 3028, 1685, 1257, 1177, 698; HRMS (ESI) m/zcalcd. for C₁₃H₁₃NO [M+H]⁺: 200.1070, found: 200.1066.

[Example 41] Preparation of 5-(prop-1-yn-1-yl)pyrrolidin-2-one (28)

Catalyst J (11.8 mg, 10 mol %) and NaBAr^(F) ₄ (17.7 mg, 10 mol %) wereused. White solid (15 mg, 61%); m.p. 77-79° C.; ¹H NMR (600 MHz, CDCl₃)δ 6.23 (s, 1H), 4.36-4.28 (m, 1H), 2.49-2.34 (m, 2H), 2.34-2.24 (m, 1H),2.16-2.06 (m, 1H), 1.80 (s, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 177.8, 80.4,78.3, 45.2, 29.7, 29.4, 3.6; IR (cm⁻¹) 3165, 3075, 1688, 1257, 777, 675,495; HRMS (EI) m/z calcd. for C₇H₉NO [M]⁺: 123.0684, found: 123.0685.

[Example 42] Preparation of trans-4-Ethyl-5-phenylpyrrolidin-2-one (29)

Catalyst J (2.4 mg, 2 mol %) was used. White solid (34 mg, 90%); >20:1d.r. and 12.6:1 r.r. were confirmed by ¹H NMR spectroscopy; m.p.131-133° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.39-7.32 (m, 2H), 7.32-7.27 (m,3H), 6.46 (s, 1H), 4.28 (d, J=6.7 Hz, 1H), 2.69-2.49 (m, 1H), 2.17-2.06(m, 2H), 1.74-1.58 (m, 1H), 1.50-1.35 (m, 1H), 0.89 (t, J=7.4 Hz, 3H);¹³C NMR (100 MHz, CDCl₃) δ 177.6, 141.6, 128.7, 127.9, 126.2, 64.1,47.0, 36.4, 26.0, 11.9; IR (cm⁻¹) 3211, 2959, 1690, 1455, 1282, 755,699; HRMS (FAB) m/z calcd. for C₁₂H₁₅NO [M+H]⁺: 190.1232, found:190.1230.

[Example 43] Preparation of 4-benzyl-5,5-dimethylpyrrolidin-2-one(30-A)/trans-4-Isopropyl-5-phenylpyrrolidin-2-one (30-B)

Catalyst J (2.4 mg, 2 mol %) was used. Combined isolated yield: 96% (39mg). 1.3:1 r.r was confirmed by ¹H NMR spectroscopy.

4-Benzyl-5,5-dimethylpyrrolidin-2-one (30-A)

Major regioisomer: White solid (22 mg); m.p. 124-126° C.; ¹H NMR (400MHz, CDCl₃) δ 7.29 (t, J=7.4 Hz, 2H), 7.21 (t, J=7.3 Hz, 1H), 7.16 (d,J=7.2 Hz, 2H), 6.66 (s, 1H), 2.81 (dd, J=13.3, 4.6 Hz, 1H), 2.52 (dd,J=13.2, 10.6 Hz, 1H), 2.43-2.33 (m, 1H), 2.28-2.12 (m, 2H), 1.26 (s,3H), 1.22 (s, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 176.0, 139.7, 128.6,128.6, 126.3, 58.8, 47.5, 36.5, 35.9, 28.4, 23.5; IR (cm⁻¹) 3217, 2966,1691; HRMS (FAB) m/z calcd. for C₁₃H₁₇NO [M+H]⁺: 204.1388, found:204.1387.

trans-4-Isopropyl-5-phenylpyrrolidin-2-one (30-B)

Minor regioisomer: Colorless oil (17 mg); >20:1 d.r. was confirmed by ¹HNMR spectroscopy; ¹H NMR (400 MHz, CDCl₃) δ 7.43-7.33 (m, 2H), 7.32-7.26(m, 3H), 6.17 (s, 1H), 4.43 (d, J=5.7 Hz, 1H), 2.55-2.44 (m, 1H),2.25-2.16 (m, 2H), 1.85-1.75 (m, 1H), 0.96 (d, J=6.7 Hz, 3H), 0.86 (d,J=6.8 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 177.4, 142.4, 128.8, 127.9,126.4, 61.7, 50.8, 33.0, 30.1, 20.8, 18.8; IR (cm⁻¹) 3209, 2957, 1694,700; HRMS (FAB) m/z calcd. for C₁₃H₁₇NO [M+H]⁺: 204.1388, found:204.1389.

[Example 44] Preparation of(S)-2-(5,5-dimethyl-2-oxopyrrolidin-3-yl)isoindoline-1,3-dione (31)

Using Catalyst K (5.9 mg, 5 mol %) and NaBAr^(F) ₄ (8.8 mg, 5 mol %).White solid (29 mg, 56%); m.p. 217-219° C.; ¹H NMR (400 MHz, CDCl₃) δ7.85 (dd, J=5.4, 3.1 Hz, 2H), 7.72 (dd, J=5.5, 3.1 Hz, 2H), 5.86 (s,1H), 5.13-5.05 (m, 1H), 2.44 (t, J=11.6 Hz, 1H), 2.33 (dd, J=12.4, 9.3Hz, 1H), 1.47 (s, 3H), 1.38 (s, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 170.6,167.5, 134.1, 131.9, 123.5, 53.6, 49.7, 39.5, 29.9, 29.3; IR (cm⁻¹)3180, 3087, 1701, 1387, 716; HRMS (EI) m/z calcd. for C₁₄H₁₄N₂O₃ [M]⁺:258.1004, found: 258.1007; Optical Rotation: [a]²⁸ _(D)=−60 (c=1.0,CHCl₃); HPLC Analysis (250 mm CHIRALPAK AD-H column, 20% i-PrOH/hexanes,0.8 mL/min, 254 nm, 25° C.) indicated 99% ee:t_(R)(major)=35.2 min,t_(R) (minor)=11.1 min.

[Example 45] Preparation of2-((3S,5S)-2-oxo-5-phenylpyrrolidin-3-yl)isoindoline-1,3-dione (32)

Using Catalyst K (5.9 mg, 5 mol %) and NaBAr^(F) ₄ (8.8 mg, 5 mol %).White solid (29 mg, 48%); ¹H NMR spectroscopic analysis of theunpurified reaction mixture indicated 10:1 dr; m.p. 260-262° C.; ¹H NMR(600 MHz, CDCl₃) δ 7.89-7.81 (m, 2H), 7.76-7.70 (m, 2H), 7.53 (d, J=7.4Hz, 2H), 7.41 (t, J=7.6 Hz, 2H), 7.34 (t, J=7.5 Hz, 1H), 6.28 (s, 1H),5.09 (t, J=10.3 Hz, 1H), 4.74 (t, J=8.1 Hz, 1H), 2.90-2.80 (m, 1H),2.61-2.45 (m, 1H); ¹³C NMR (150 MHz, CDCl₃) δ 172.0, 167.6, 141.2,134.4, 132.1, 129.2, 128.7, 126.8, 123.7, 55.2, 50.2, 36.3; IR (cm⁻¹)3356, 2923, 1710, 1390, 718; HRMS (EI) m/z calcd. for C₁₈H₁₄N₂O₃ [M]⁺:306.1004, found: 306.1007; Optical Rotation: [a]² _(D)=−34 (c=1.0,CHCl₃); HPLC Analysis (250 mm CHIRALPAK AD-H column, 20% i-PrOH/hexanes,0.8 mL/min, 254 nm, 25° C.) indicated 98% ee: t_(R) (major)=41.8 min,t_(R) (minor)=27.7 min.

[Example 46] Preparation of(R)-2-(2,2-dimethyl-5-oxopyrrolidin-3-yl)isoindoline-1,3-dione (33)

Using Catalyst K (5.9 mg, 5 mol %) and NaBAr^(F) ₄ (8.8 mg, 5 mol %).White solid (28 mg, 55%); m.p. 172-174° C.; ¹H NMR (600 MHz, CDCl₃) δ7.85 (dd, J=5.5, 3.1 Hz, 2H), 7.74 (dd, J=5.5, 3.1 Hz, 2H), 6.84 (s,1H), 4.73 (dd, J=9.4, 5.9 Hz, 1H), 3.32 (dd, J=17.2, 5.9 Hz, 1H), 2.75(dd, J=17.2, 9.4 Hz, 1H), 1.42 (s, 3H), 1.20 (s, 3H); ¹³C NMR (150 MHz,CDCl₃) δ 174.2, 168.4, 134.5, 131.6, 123.7, 60.2, 55.3, 33.0, 29.6,24.1; IR (cm⁻¹) 2962, 1830, 1710, 1371, 712; HRMS (EI) m/z calcd. forC₁₄H₁₄N₂O₃ [M]⁺: 258.1004, found: 258.1005; Optical Rotation: [a]²⁸_(D)=33 (c=1.0, CHCl₃); HPLC Analysis (250 mm CHIRALCELOD-Hcolumn, 20%i-PrOH/hexanes, 0.8 mL/min, 254 nm, 25° C.) indicated 99% ee: t_(R)(major)=31.0 min,t_(R) (minor)=24.8 min.

[Example 47] Preparation of2-((2-oxooctahydro-3aH-indol-3a-yl)methyl)isoindoline-1,3-dione (34)

Using Catalyst K (5.9 mg, 5 mol %) and NaBAr^(F) ₄ (8.8 mg, 5 mol %).White solid (53 mg, 88%); m.p. 174-176° C.; ¹H NMR (400 MHz, CDCl₃) δ7.86 (dd, J=5.5, 3.1, 2H), 7.75 (dd, J=5.5, 3.1 Hz, 2H), 5.52 (s, 1H),3.79 (d, J=0.8 Hz, 2H), 3.58 (t, J=4.0 Hz, 1H), 2.48 (d, J=16.4, 1H),2.03 (d, J=16.4 Hz, 1H), 1.94-1.82 (m, 1H), 1.72-1.64 (m, 1H), 1.60-1.42(m, 6H); ¹³C NMR (100 MHz, CDCl₃) δ 176.7, 169.0, 134.4, 131.9, 123.7,55.5, 43.2, 43.1, 42.6, 30.8, 26.5, 21.2, 20.0; IR (cm⁻¹) 3218, 2931,1772, 1708, 1394, 724; HRMS (EI) m/z calcd. for C₁₇H₁₈N₂O₃ [M]⁺:298.1317, found: 298.1318.

[Example 48] Preparation of cis-tert-butyl{(2-oxooctahydro-3aH-indol-3a-yl)methyl}carbamate (35)

Using Catalyst K(5.9 mg, 5 mol %) and NaBAr^(F) ₄ (8.8 mg, 5 mol %) in asolvent of hexafluoro-2-propanol (2.4 mL); Beige solid (24 mg, 45%);m.p. 62-64° C.; ¹H NMR (400 MHz, CDCl₃) 55.96 (s, 1H), 4.72 (s, 1H),3.46 (t, J=3.8 Hz, 1H), 3.31-3.09 (m, 2H), 2.24 (d, J=16.2 Hz, 1H), 1.99(d, J=16.2 Hz, 1H), 1.76-1.54 (m, 2H), 1.53-1.34 (m, 15H); ¹³C NMR (100MHz, CDCl₃) 5177.0, 156.2, 79.6, 55.3, 45.0, 42.4, 42.0, 30.0, 28.3,26.8, 21.0, 20.0; IR (cm⁻¹) 3279, 2929, 1681, 1526, 1365, 1249, 1166,1008, 918, 730; HRMS (FAB) m/z calcd. for C₁₄H₂₄N₂O₃ [M+H]⁺: 269.1865,found: 269.1862.

[Example 49] Preparation of tert-butyl2-methyl-5-oxopyrrolidine-1-carboxylate (36)

5-Methylpyrrolidin-2-one was separated by one-pot Boc-protection andthen prepared.

The catalytic reaction mixture of 3-butyl-1,4,2-dioxazol-5-one wascooled to room temperature, di-tert-butyl dicarbonate (Boc₂O, 91.9 μL0.4 mmol), 4-(dimethylamino)pyridine (DMAP, 24.4 mg, 0.2 mmol), andtriethylamine (27.8 μL, 0.2 mmol) were added thereto and the mixture wasvigorously stirred at room temperature for 12 hours. The reactionmixture was filtered with celite, washed with dichloromethane (10 mL×4),and concentrated under reduced pressure to obtain a residue, which wasseparated and purified by column chromatography (eluent: n-hexane/EtOAc,2:1˜1:2) to obtain the desired compound.

The compound prepared by the above method is shown in the following.

Yellowish oil (22 mg, 55%); ¹H NMR (600 MHz, CDCl₃) δ 4.28-4.18 (m, 1H),2.60 (dt, J=19.8, 10.0 Hz, 1H), 2.42 (ddd, J=17.6, 9.4, 2.7 Hz, 1H),2.16 (dt, J=20.6, 9.9 Hz, 1H), 1.66-1.61 (m, 1H), 1.52 (s, 9H), 1.31 (d,J=6.3 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 174.2, 149.9, 82.6, 54.0, 31.328.0, 25.2, 20.2.

[Examples 50 to 58, and Comparative Examples 3 to 7] Preparation ofGamma-Lactam Compound

A gamma-lactam compound was prepared in the same manner as in Example19, except that the catalyst and time were different as shown in Table1, and the results are shown in Table 1.

TABLE 1 Reaction Yield (%) of Yield of Mole Catalyst NaBAr₄ ^(F)temperature, T Reaction gamma-lactam Compound ratio of (mol %) (mol %)(° C.) time (h) compound (1) 1-a 1:1-a Example 50 Complex D NaBAr₄ ^(F)rt 18 73 14 5.2:1 (10 mol %) (10 mol %) Example 51 Complex E NaBAr₄ ^(F)rt 18 81 17 4.8:1 (10 mol %) (10 mol %) Example 52 Complex F NaBAr₄ ^(F)rt 12 86 13 6.2:1 (10 mol %) (10 mol %) Example 53 Complex G NaBAr₄ ^(F)rt 12 90 9 9.8:1 (10 mol %) (10 mol %) Example 54 Complex I NaBAr₄ ^(F)rt 24 80 8 9.5:1 (10 mol %) (10 mol %) Example 55 Complex J NaBAr₄ ^(F)rt 2 97 <5 >20:1 (10 mol %) (10 mol %) Example 56 Complex K NaBAr₄ ^(F)rt 6 98 <5 >20:1 (10 mol %) (10 mol %) Example 57 Complex L NaBAr₄ ^(F)rt 6 98 <5 >20:1 (10 mol %) (10 mol %) Example 58 Complex J NaBAr₄ ^(F)rt 12 94 <5 >20:1  (2 mol %)  (2 mol %) Comparative Complex A NaBAr₄^(F) 60 12 39 17 2.3:1 Example 3 (10 mol %) (10 mol %) ComparativeComplex B NaBAr₄ ^(F) 40 18 73 15 4.8:1 Example 4 (10 mol %) (10 mol %)Comparative Rh₂(OAc)₄ ^(b) — 40 12 <5 <5 — Example 5  (5 mol %)Comparative Rh₂(esp)₂ ^(b) — 40 12 <5 <5 — Example 6  (5 mol %)Comparative Ru(TPP)CO^(b) NaBAr₄ ^(F) 40 12 <5 35 — Example 7  (5 mol %) (5 mol %) rt: room temperature, ^(b)The catalyst of Comparative Example5-7 was purchased from Aldrich and TCl.

As shown in Table 1 above, the catalyst which is the metal complexhaving a specific ligand of the present invention produced a lactamcompound with surprisingly excellent selectivity and yield as comparedwith the catalysts of Comparative Examples 3 to 7.

Furthermore, with the metal catalyst of the present invention, thereaction is performed under mild conditions and simultaneously, agamma-lactam compound may be obtained with a high yield and excellentselectivity, and the method of preparing a gamma-lactam compound of thepresent invention may be very usefully applied to a raw material and anintermediate such as various natural products and medicines.

Example III: Application of Method of Preparing Gamma-Lactam Compound ofthe Present Invention [Example 59] Preparation of(Z)-6a-(pent-2-en-1-yl)hexahydrocyclopenta[b]pyrrole-2,6-dione

(Z)-6a-(Pent-2-en-1-yl)hexahydrocyclopenta[b]pyrrole-2,6-dione wasprepared in the same manner as in Example 19, except that the startingmaterial was different.

Preparation was performed by stirring at 40° C. for 12 hours andstirring again at 80° C. for 12 hours, using Catalyst J (11.8 mg, 10 mol%) and NaBAr^(F) ₄ (17.7 mg, 10 mol %). Colorless oil (29 mg, 70%); ¹HNMR (400 MHz, CDCl₃) δ 5.69 (s, 1H), 5.62 (dt, J=10.9, 7.4 Hz, 1H),5.35-5.18 (m, 1H), 2.82-2.62 (m, 2H), 2.52 (ddd, J=18.1, 8.1, 4.5 Hz,1H), 2.41-2.15 (m, 5H), 2.05 (p, J=7.7 Hz, 2H), 1.76-1.63 (m, 1H), 0.97(t, J=7.5 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 214.9, 175.8, 137.2,120.2, 67.9, 38.9, 37.2, 36.9, 32.2, 26.0, 20.7, 14.0; IR (cm⁻¹) 3214,2961, 2932, 2872, 1739, 1686; HRMS (EI) m/z calcd. for C₁₂H₁₇NO₂ [M]⁺:207.1259, found: 207.1258.

[Example 60] Preparation of (5S)-5-((3R,5R,9S,10S,13S,14S)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-5-methylpyrrolidin-2-one

Prepared with Catalyst K (5.9 mg, 5 mol %) and NaBAr^(F) ₄ (8.8 mg, 5mol %). White solid (26 mg, 32%); m.p. 231-233° C.; ¹H NMR (600 MHz,CDCl₃) δ 5.57 (s, 1H), 3.35 (s, 3H), 3.16 (tt, J=10.5, 4.6 Hz, 1H), 2.37(dt, J=18.1, 8.8 Hz, 1H), 2.31-2.21 (m, 1H), 2.12-1.98 (m, 2H),1.90-1.81 (m, 1H), 1.80-1.54 (m, 10H), 1.36 (d, J=21.9 Hz, 7H),1.29-1.16 (m, 4H), 1.14-1.02 (m, 3H), 0.98-0.85 (m, 4H), 0.73 (s, 3H);¹³C NMR (150 MHz, CDCl₃, one carbon merged to others) δ 177.6, 80.3,61.7, 59.6, 56.3, 55.6, 43.5, 41.9, 40.2, 35.3, 35.2, 34.8, 34.8, 32.7,29.1, 28.7, 27.2, 26.8, 26.2, 23.7, 23.3, 23.0, 20.5, 13.6; IR (cm⁻¹)3230, 2925, 2862, 1689, 1448, 1369, 1098; HRMS (EI) m/z calcd. forC₂₅H₄₁NO₂ [M]⁺: 387.3137, found: 387.3139.

[Example 61] Preparation of(±)-trans-4-Methyl-5-(3-methylbut-2-en-1-yl)pyrrolidin-2-one

Prepared with Catalyst K (5.9 mg, 5 mol %) and NaBAr^(F) ₄ (8.8 mg, 5mol %). Colorless oil (15 mg, 45%); ¹H NMR spectroscopic analysis of theunpurified reaction mixture indicated 3.4:1 dr; major isomer (antidiastereomer); ¹H NMR (400 MHz, CDCl₃) δ 5.68 (s, 1H), 5.08 (t, J=7.9Hz, 1H), 3.18 (dt, J=8.3, 5.7 Hz, 1H), 2.51 (dd, J=16.6, 8.3 Hz, 1H),2.30-2.18 (m, 1H), 2.17-2.07 (m, 2H), 1.99 (dt, J=16.5, 8.0 Hz, 1H),1.71 (s, 3H), 1.62 (s, 3H), 1.12 (d, J=6.7 Hz, 3H); ¹³C NMR (150 MHz,CDCl₃) δ 176.9, 135.4, 119.4, 61.9, 38.8, 35.4, 33.8, 25.8, 18.9, 18.0;IR (cm⁻¹) 3213, 2961, 2923, 1686, 1376; HRMS (EI) m/z calcd. forC₁₀H₁₇NO [M]⁺: 167.1310, found: 167.1312.

[Example 62] Preparation of(3S,3aS,5aS,9bR)-3,5a,9-Trimethyl-1,3a,4,5,5a,9b-hexahydro-2H-benzo[g]indole-2,8(3H)-dione

Prepared with Catalyst K (11.8 mg, 10 mol %), NaBAr^(F) ₄ (17.7 mg, 10mol %), and chloroform (2.4 mL) as a solvent. White solid (21 mg, 43%);¹H NMR spectroscopic analysis of the unpurified reaction mixtureindicated >20:1 dr; m.p. 299-301° C.; ¹H NMR (600 MHz, CDCl₃) 6.73 (d,J=9.8 Hz, 1H), 6.24 (d, J=9.8 Hz, 1H), 5.50 (s, 1H), 4.90 (d, J=5.5 Hz,1H), 2.32-2.25 (m, 1H), 2.14-2.07 (m, 1H), 2.02 (s, 3H), 1.84-1.79 (m,2H), 1.78-1.70 (m, 1H), 1.49-1.38 (m, 1H), 1.33 (s, 3H), 1.30 (d, J=7.5Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 186.1, 180.8, 157.6, 151.6, 135.9,125.9, 52.8, 44.9, 43.6, 39.6, 34.8, 25.7, 23.6, 15.0, 11.2; IR (cm 1)3181, 2948, 1696, 1651, 1624, 1271, 853, 769; HRMS (EI) m/z calcd. forC₁₅H₁₉NO₂ [M]⁺: 245.1416, found: 245.1417.

As seen from Examples 59 to 62, it was found that the method ofpreparing a gamma-lactam compound from a dioxazol-one compound which wasan intentionally selected starting material, using the metal complex ofthe present invention as a catalyst may be very useful in preparation ofan intermediate and a raw material of synthesis of medicines, naturalmaterials, and the like.

1. A method of preparing a gamma-lactam compound, the method comprising:amidating a dioxazol-one compound in the presence of a metal complexrepresented by the following Chemical Formula 1 and a base to preparethe gamma-lactam compound:

wherein M is iridium, rhodium, ruthenium, or cobalt; L is

X is a halogen; R₁ to R₅ are independently of one another hydrogen or(C1-C20)alkyl; and R₆ is a halogen, (C1-C20)alkyl, halo(C1-C20)alkyl,(C1-C20)alkoxy, (C6-C20)aryl, or (C3-C20)heteroaryl; A is —CO— or —SO₂—;R₇ is (C1-C20)alkyl, (C1-C20)alkoxy, (C6-C20)aryl,(C1-C20)alkyl(C6-C20)aryl, or —NR₁₁R₁₂; R₁₁ and R₁₂ are independently ofeach other hydrogen or (C1-C20)alkyl; and n is an integer of 0 to
 6. 2.The method of preparing a gamma-lactam compound of claim 1, wherein thedioxazol-one compound is represented by the following Chemical Formula 4and the gamma-lactam compound is represented by the following ChemicalFormula 5:

wherein R_(a1) to R_(a6) are independently of one another hydrogen,(C1-C20)alkyl, (C3-C20)cycloalkyl, (C2-C20)alkenyl, (C2-C20)alkynyl,(C1-C20)alkoxy, (C6-C20)aryl, (C3-C20)heteroaryl, or(C3-C20)heterocycloalkyl, or may be connected to an adjacent substituentto form an aromatic ring, an alicyclic ring, or spiro ring with orwithout a fused ring; the alkyl, the cycloalkyl, the alkenyl, thealkynyl, the alkoxy, the aryl, the heteroaryl, the aromatic ring, thealicyclic ring, or the spiro ring of R_(a1) to R_(a6) may be furthersubstituted by any one or more substituents selected from a halogen,nitro, cyano, (C1-C20)alkyl, (C1-C20)alkenyl, (C1-C20)alkoxy,(C6-C20)aryl, (C6-C20)aryl(C1-C20)alkyl, (C3-C20)heteroaryl,(C3-C20)heterocycloalkyl, and —N(R_(a11)) (R_(a12)); and R_(a11) andR_(a12) are independently of each other hydrogen, (C1-C20)alkyl, or(C1-C20)alkoxycarbonyl.
 3. The method of preparing a gamma-lactamcompound of claim 1, wherein the metal complex is used at 0.01 to 0.1mol with respect to 1 mol of the dioxazol-one compound.
 4. The method ofpreparing a gamma-lactam compound of claim 1, wherein the base is one ortwo or more selected from NaBAr^(F) ₄ (sodium tetrakis [3,5-bis(trifluoromethyl)phenyl]borate), AgSbF₆ (silverhexafluoroantimonate(V)), AgNTf₂ (silverbis(trifluoromethanesulfonyl)imide), AgBF₄ (silver tetrafluoroborate),AgPF₆ (silver hexafluorophosphate), AgOTf (silvertrifluoromethanesulfonate), and AgOAc (silver acetate).
 5. The method ofpreparing a gamma-lactam compound of claim 1, wherein the base is usedat 0.01 to 0.1 mol with respect to 1 mol of the dioxazol-one compound.6. The method of preparing a gamma-lactam compound of claim 1, whereinthe amidating is performed at 20 to 60° C.
 7. The method of preparing agamma-lactam compound of claim 1, wherein in Chemical Formula 1, M isiridium; L is

X is chloro; R₁ to R₅ are independently of one another (C1-C20)alkyl; R₆is (C1-C20)alkoxy; A is —CO—; R₇ is (C1-C20)alkoxy; and n is an integerof 0 or
 1. 8. The method of preparing a gamma-lactam compound of claim2, wherein R_(a1) to R_(a5) are independently of each other hydrogen,(C1-C20)alkyl, or (C3-C20)heterocycloalkyl; R_(a6) is independently ofeach other hydrogen, (C1-C20)alkyl, (C3-C20)cycloalkyl, (C2-C20)alkenyl,(C2-C20)alkynyl, (C6-C20)aryl, or (C3-C20)heteroaryl, or R_(a5) andR_(a6) may be connected to form a (C5-C8)spiro ring, R_(a2) and R_(a3)may be connected by (C2-C10)alkenylene to form a (C6-C12)aromatic ring,and in this case, R_(a1) and R_(a2) are not present, R_(a3) and R_(a6)may be connected to each other to form a (C3-C20)alicyclic ring with orwithout an aromatic ring, R_(a3) and R_(a4) and R_(a6) may be connectedto each other to form a (C3-C20)alicyclic ring with or without anaromatic ring, the alkyl of R_(a1) to R_(a5), and the alkyl, thecycloalkyl, the alkenyl, the alkynyl, the aryl, or the heteroaryl ofR_(a6) may be further substituted by any one or more substituentsselected from a halogen, nitro, cyano, (C1-C20)alkyl, (C1-C20)alkenyl,(C1-C20)alkoxy, (C6-C20)aryl, (C6-C20)aryl(C1-C20)alkyl,(C3-C20)heterocycloalkyl, and —N (R_(a11)) (R_(a12)); and R_(a11) andR_(a12) are independently of each other hydrogen, (C1-C20)alkyl, or(C1-C20)alkoxycarbonyl.
 9. The method of preparing a gamma-lactamcompound of claim 1, wherein amidating a dioxazol-one compound of thefollowing Chemical Formula 6 in the presence of the compound representedby Chemical Formula 1 and the base to prepare a gamma-lactam compound ofthe following Chemical Formula 7 is included:

wherein R_(a1) and R_(a3) are independently of each other hydrogen,(C1-C20)alkyl, or (C3-C20)heterocycloalkyl; R_(a2) and R_(a5) areindependently of each other hydrogen or (C1-C20)alkyl; R_(a6) is(C1-C20)alkyl, (C3-C20)cycloalkyl, (C2-C20)alkenyl, (C2-C20)alkynyl,(C6-C20)aryl, or (C3-C20)heteroaryl; the alkyl, the cycloalkyl, thealkenyl, the alkynyl, the aryl, and the heteroaryl of R_(a6) may befurther substituted by any one or more substituents selected from ahalogen, nitro, cyano, (C1-C20)alkyl, (C2-C20)alkenyl, (C1-C20)alkoxy,(C6-C20)aryl, (C6-C20) aryl (C1-C20) alkyl, and —N(R_(a11)) (R_(a12));and R_(a11) and R_(a12) are independently of each other hydrogen,(C1-C20)alkyl, or (C1-C20)alkoxycarbonyl.
 10. The method of preparing agamma-lactam compound of claim 1, wherein amidating a dioxazol-onecompound of the following Chemical Formula 8 in the presence of thecompound represented by Chemical Formula 1 and the base to prepare agamma-lactam compound of the following Chemical Formula 9 is included:

wherein ring A is a (C3-C20)alicyclic ring with or without an aromaticring; R_(a1) and R_(a3) are independently of one another hydrogen or(C1-C20)alkyl; R_(a5) is hydrogen or (C2-C20)alkenyl; the alkyl ofR_(a1) and R_(a3) and the alkenyl of R_(a5) may be further substitutedby any one or more substituents selected from a halogen, nitro, cyano,(C1-C20)alkyl, (C2-C20)alkenyl, (C1-C20)alkoxy, (C6-C20)aryl, (C6-C20)heteroaryl, (C3-C20)heterocycloalkyl, and —N(R_(a21)) (R_(a22)); andR_(a21) and R_(a22) are independently of each other hydrogen,(C1-C20)alkyl, or (C1-C20)alkoxycarbonyl.
 11. The method of preparing agamma-lactam compound of claim 1, wherein amidating a dioxazol-onecompound of the following Chemical Formula 10 in the presence of thecompound represented by Chemical Formula 1 and the base to prepare agamma-lactam compound of the following Chemical Formula 11 is included:

wherein R_(a1) to R_(a3) are independently of one another hydrogen or(C1-C20)alkyl; ring B is an alicyclic ring; and the alkyl of R_(a1) toR_(a3) and the alicyclic ring of ring B may be further substituted byany one or more substituents selected from a halogen, nitro, cyano,(C1-C20)alkyl, (C2-C20)alkenyl, (C1-C20)alkoxy, (C6-C20)aryl, and(C6-C20)aryl(C1-C20)alkyl.
 12. The method of preparing a gamma-lactamcompound of claim 1, wherein amidating a dioxazol-one compound of thefollowing Chemical Formula 12 in the presence of the compoundrepresented by Chemical Formula 1 and the base to prepare a gamma-lactamcompound of the following Chemical Formula 13 is included:

wherein R_(a5) and R_(a6) are independently of each other hydrogen,(C1-C20)alkyl, or (C6-C20) aryl.